Edinburgh, 1828. An elderly apple-seller runs into two familiar figures on the street: Mr William Burke and Billy Hare. But Burke and Hare have a different sort of business to conduct, and there’s nobody else around to hear her scream... Some time later, Hare arrives at the pub known as the Last Drop with coins in his pocket, and finds local Mary Patterson speaking with the halfwit known as Daft Jamie. Mary has a soft spot for the innocent Jamie, but Hare just finds him disgusting. However, Mary feels the same about Hare; she may have run out of money for gin and whisky, but she’s not desperate enough to sell her services to Hare. She sets off into the thick fog to find another client, while Hare waits, confident that her thirst will soon be strong enough to drive her into his arms.

The Doctor is tinkering with the TARDIS console again, and Evelyn is equally amused and exasperated by the fact that he seems fonder of his ship than of his human companions. When the TARDIS materialises, it does so with unaccustomed smoothness, and the Doctor notes that the scanner is completely black. Despite his concern, however, Evelyn talks him into investigating. They’ve materialised underground, in the pitch black of a city’s drainage system, and they soon find their way out of the tunnels into a market, where the Doctor runs into Mary. Though irritated to see that the Doctor already has a female companion, she tries to chat him up nonetheless, and invites him to stop by the Last Drop if he wishes to see her again. She then finds that Daft Jamie has followed her from the pub, and takes him to task for interfering in her business. Meeting a Scots lad named Jamie reminds the Doctor of his former companion, and as he reminisces fondly over his friend, Daft Jamie is delighted, believing that the Doctor has heard of him and that he’s going to be famous. As it happens, this is indeed the case, as the Doctor realises when the departing Mary actually calls “Daft Jamie” by his full nickname. As Mary and Jamie depart, Evelyn points out a disturbing bloodstain in the gutter, confirming the delighted Doctor’s suspicions; he now knows exactly where they are and when, or so he thinks...

Mary returns to the Last Drop, but orders Jamie to stay outside. Hare is delighted to see her, but a few minutes in Hare’s company is all she can take, and when Jamie disobeys and enters the pub to look for his friend, she calls him over. Hare prepares to take his leave, but pulls up sharply when Daft Jamie announces aloud that a strange man in the marketplace was looking at the blood. Shaken, Hare threatens to slit Mary’s throat unless she tells him everything, and, somewhat frightened, she tells him about her encounter with the “English gentleman”. Disturbed to learn that there are strangers about, Hare storms off to the bar, but on the way he bumps into a familiar figure -- not literally, however, as the man doesn’t like to make physical contact with his employees. Dr Robert Knox has come to the bar incognito to speak with Hare, and when Hare warns him that there are strangers in town, Knox expresses surprise in an overly theatrical manner; in truth, however, he isn’t that interested in the news.

Evelyn still doesn’t know exactly where they are, and doesn’t understand why the Doctor has taken her to Greyfriars Graveyard to look for freshly dug graves. They soon find a mound of earth piled beside a grave with an exposed coffin inside. This coffin has not been buried, but disinterred, and it confirms the Doctor’s suspicions that they’ve arrived in Edinburgh in the right era to meet Burke and Hare, the infamous bodysnatchers and serial killers. The Doctor intends to meet them so he can drop their names into conversations in the future. Evelyn is less interested in meeting two such notorious murderers, but the Doctor points out that their crimes contributed indirectly to the sum of human medical knowledge; he does not condone their activities, but, grim as they are, he can look at the big picture and see that the murders in Edinburgh will, one day, save many more lives and make the universe a slightly better place.

Hare visits Dr Knox’s home in person to warn him about the Doctor, and finds him writing an entry in his diary and speaking aloud as he does so. Disturbed by the Doctor’s unnatural knowledge and irritated by Knox’s arrogance, Hare threatens to reveal what he’s been doing for Knox, but Knox laughs off Hare’s threats of blackmail and sends him on his way. Though interested by the fact that this Doctor somehow knows of the existence of William Burke, Knox dismisses the curiosity for the moment and returns to his surgery to begin his latest round of autopsies. He speaks aloud as he works, as though narrating his actions for an unseen audience.

Back in the Last Drop, the Doctor is having trouble recalling the exact timeline of the Burke and Hare murders; nevertheless, he does conclude that Mary must certainly know Burke by this time. However, she doesn’t, and the Doctor’s strange questions and his familiarity with Hare are beginning to frighten her. The Doctor asks Daft Jamie to lead him to Hare’s boarding house, and asks Mary to show Evelyn to Dr Knox’s house; at least Mary has heard of him, though only by reputation. Mary is reluctant to get involved, despite the Doctor’s claim that she’s destined to play a role in these events, but she caves in when she sees how excited Daft Jamie is to be helping in something important. Mary and Evelyn thus set off for Dr Knox’s house, though Evelyn isn’t sure what the Doctor wants her to do there and Mary is sure that they’ll never gain admittance to a rich doctor’s private lodgings.

Daft Jamie leads the Doctor to Hare’s lodging house, where Hare answers the door in a foul temper. The Doctor manages to calm him down, insisting that he’s a man of medicine who genuinely appreciates the work Hare has done. Hare admits that he’s in it mainly for the money, but claims that his own children died young and that he appreciates the chance to serve medical science. But when the Doctor tries to turn the topic of conversation back to Burke, Hare slams the door in his face. The Doctor sets off back to the Last Drop empty-handed, but Daft Jamie turns down the Doctor’s offer to buy him a drink; he doesn’t drink, any more than he likes Mr Burke. It takes the Doctor a moment to realise that this was not a slip of the tongue; Daft Jamie really has met Burke before, and according to him, so has Mary...

Mary and Evelyn arrive at Dr Knox’s house, and when they find the front door open, Evelyn decides to enter uninvited. As they wait in Knox’s sitting room, Evelyn notes that Mary seems ill at ease in these opulent surroundings, and assures the self-deprecating Mary that she does indeed have an important part to play in history -- albeit, she must admit, an unpleasant one. Knox himself then arrives, but refuses to shake hands with his visitors and orders them out of his home. Irritated by his arrogant and cruel attitude, Evelyn asks him some pointed questions about his work with the less fortunate and his associate with Burke, but Knox doesn’t take the bait. He does, however, confirm that he’s been cutting up cadavers in the name of medical research, and he’s proud of it. Mary is repulsed, but he’s just as repulsed by her lifestyle, pointing out that her alcoholism and her work as a prostitute expose her to virulent diseases that he could cure if only he were legally allowed to conduct research into the human anatomy. Though Evelyn claims to have been sent by a doctor, Knox refers to himself as the Jekyll to this other Doctor’s Hyde. Evelyn storms out with Mary, tartly informing Knox that, as far as she’s concerned, it’s the other way around.

Mary and Evelyn return to the Last Drop, where they find the Doctor haranguing the distressed Daft Jamie for more information. When he takes Mary to task for lying to him, she has no idea what he’s talking about; Daft Jamie may claim that she knows Burke, but there’s a reason for his nickname, after all. Even now, he’s claiming that Burke and Knox both “drift in and out,” whatever that means. As the Doctor tries to work out what’s going on, Mary learns that he and Evelyn have found evidence of bodysnatching, and is repulsed when the Doctor shows no concern for the crime; as far as he’s concerned, the bodies in the graves are empty, dead flesh, and he’s far more concerned with the fact that nobody but Daft Jamie seems to be the only one who’s ever heard of William Burke.

Daft Jamie also seems to have seen a body, but this time Mary can confirm what he’s talking about; an old woman from outside the city was recently murdered in the cattle market where she first met the Doctor. This fits in with the Doctor’s knowledge of events -- an old woman from London was arrested by the police, and then murdered after they released her -- but he then learns that the old woman’s body was taken by the police, as was the body of a travelling salesman found dead in Hare’s lodging house. This doesn’t make sense at all; Burke and Hare killed their victims in order to deliver the bodies to Knox, and if the bodies have not in fact been delivered to Knox, this means people are dying for no reason at all. And yet, according to Evelyn, Knox claimed that he was still getting a steady supply of bodies. However, when she mentions Knox’s reference to Jekyll and Hyde, the Doctor is appalled and rushes off to confront Knox, leaving Daft Jamie at the pub but dragging the bewildered Evelyn and Mary along with him. Robert Louis Stevenson has yet to be born, let alone write Dr. Jekyll and Mr. Hyde -- and the fact that Knox so casually dropped an anachronism into conversation implies that he was deliberately testing Evelyn. And since she indicated to him that she understood the reference, now Knox must know that she and the Doctor are more than they seem.

Hare speaks with Knox again, concerned that the Doctor’s investigation will expose their activities and that Hare will end up going to the gallows. Knox is now taking the threat a bit more seriously, though he seems put out that the Doctor sent his subordinates to Knox’s house. Nevertheless, he’s certain that the Doctor will soon visit in person, and as Hare leaves, Knox begins preparing for the visit, narrating his actions aloud as he does so. While doing so, he notices that he’s out of canapés, and nips off to fetch some... taking his entire house with him. When the Doctor, Mary and Evelyn arrive in Surgeons’ Square, they find that Knox’s house has disappeared into thin air, or rather into the thick Scottish mists. Surprised, but unable to proceed any further with this line of investigation, the Doctor returns to the Last Drop with Mary and Evelyn -- and soon after they leave, Knox’s house re-materialises in the square with a familiar wheezing, groaning sound.

Once again, an elderly apple-seller runs into two familiar figures on the street -- but instead of Burke, Hare is accompanied by Dr Knox, who has decided to throw a plot twist into the experience by observing the murder in person. When Hare has finished, Knox pays him for his troubles -- because to Knox, it’s all about the money -- and reveals that he’s brought Burke back to throw the Doctor off the scent. He now informs Hare that Mary Patterson must be the next to die, and Hare is upset; in his own way, he does care for Mary. He begs Knox to speak with his employers and see if she can’t be spared, but Knox insists that it’s too late for her; she has “the problem.” Hare reluctantly accepts that if this she’s going to die in any case, he might as well get paid for it.

In the Last Drop, the Doctor questions Burke, who claims that he is sometimes haunted by strange memories like terrible dreams. When pressed further, Burke admits that he has been robbing graves with Hare, and eventually even to committing murder -- but he claims that Knox has always selected their specific victims. Burke just follows orders and collects his money, although he too admits it’s odd that they haven’t delivered their recent victims’ bodies to Knox. Disturbed, the Doctor dismisses Burke and ponders what he’s been told; if Knox doesn’t want dead bodies for his medical research, why is he ordering Burke and Hare to kill? And why does Daft Jamie seem to remember things that nobody else does? Mary, who’s been growing increasingly disturbed by the way the Doctor looks at her, demands that he tell her what he knows, and he reluctantly admits that she is destined to die; however, since Knox is playing around with destiny, there’s no reason why the Doctor can’t do so in turn. When Daft Jamie claims that Knox is back, the Doctor decides to confront him in person, but this time, Mary, Daft Jamie and Evelyn remain at the pub.

Burke is disturbed by the Doctor’s knowledge and by Hare’s recent erratic behaviour; but Hare is just as disgusted by Burke’s reliance on whisky to blot out his disturbing, mist-shrouded memories. Nevertheless, Hare informs Burke that they are to kill Mary Patterson for double pay, and is disgusted when the appalled Burke nevertheless requests his pay in advance so he can be with Mary one last time before her death.

The Doctor returns to Surgeons’ Square, and this time, Knox’s house is just where it should be -- except of course that it’s not a house, but a Type 70 TARDIS. To the Doctor’s disgust, however, Knox is not a renegade Time Lord after all, but a human who acquired his ship from a Nekkistani dealer on Gryben; it seems that the Time Lords have lost their monopoly on time-active technology while the Doctor’s back was turned. Knox claims to be engaged on a humanitarian enterprise, though he admits that he’s charging for his services. His alien clients are dying from a flu-like plague, and since their immune systems are remarkably similar to those of humans but their exterior appearance is quite different, Knox is acting as their agent on Earth, using the riff-raff of Edinburgh as human guinea pigs in his experiments. He has infected his victims with the virus and is examining their bodies to determine how to defeat the plague. Though disgusted by Knox’s callous attitude, the Doctor must admit that he is doing a rather twisted form of good deed -- and since Knox has infected Mary Patterson with the virus, she’s doomed to die in any case. If the Doctor prevents her murder, the consequences could be disastrous.

Disturbed by his conversation with Knox, the Doctor returns to the Last Drop, only to learn that there’s been a riot in his absence -- and Evelyn has been arrested for disturbing the peace. According to Mary, Hare and Burke showed up at the inn, had a few drinks, and began to fight with each other; the brawl spread, and in the confusion, Burke tried to kill Mary. Hare intervened, and then he, Burke -- and Evelyn, who’d been trying to protect Mary -- were all arrested and carted off by the police. According to Mary, Hare told the police everything that he and Burke had done. The Doctor is bewildered; this isn’t how things should be happening at all. But when he insists that Mary remain with him for her own protection, she refuses; she’s had enough of the Doctor’s cryptic and cruel claims that history says she should be dead. The Doctor is helpless to stop Mary from taking her leave of him and stalking out into the misty streets to resume her trade.

The Doctor confronts Knox once more, and this time, “Knox” admits that he’s not the real, historical Dr Knox -- and that while he did promise to help his alien clients find a cure, he’s not going to go out of his way to do so. In fact, the flu virus inexplicably failed to thrive in Edinburgh, and when he examined his victims’ bodies, he determined that the high content of alcohol in their bloodstreams had prevented it from getting a grip on them. Ironically, since Knox can’t stomach the strong drink of this era, he’s the only one vulnerable to the illness, which is why he hired Burke and Hare to commit the murders and why he refuses to make physical contact with anyone around him. However, he’d run out of subjects before he figured that out -- and, rather than draw attention to himself by carving a swathe of carnage across the world, he used his acquired technology to roll Time back and start over again with the same victims. As a profitable sideline, he’s opened up the show to the public, and is raking in the cash by selling the viewing rights to “the Burke and Hare experience” to the rich and bored elite of the galaxy. The fact that he now knows that his “experiments” are fruitless is neither here nor there, as he doesn’t particularly care that his original clients will die out when he fails to provide them with the cure as he’d promised.

Hare arrives to warn Knox that Burke tried to tell everything to Mary to save her life, and that he therefore sold Burke out to the police. Knox promises to make sure that Hare escapes from the police, and Hare leaves, satisfied with the outcome. The Doctor, disgusted, warns Knox that his tampering is putting an intolerable strain on the continuum; the people of Edinburgh are already suffering from confusion and experiencing strange dreams as they struggle to make sense of their buried memories of the previous times through the loop. The confusion and déjà vu has even taken physical form as the mists in the streets. Only Daft Jamie can recall his previous experiences, due to his general mental confusion -- but Knox reveals that he’s infected Daft Jamie with the virus in any case, and he therefore poses no threat. Knox feels no remorse for what he’s done, but as far as the Doctor’s concerned, if Knox thinks he can tamper with Time for his own benefit, then the Doctor can tamper right back at him and put an end to his crimes.

The Doctor returns to the Last Drop, where Evelyn is trying to comfort the distressed Daft Jamie. The Doctor urges them both to accompany him back to the tunnels, telling Evelyn that there’s only one way to stop Knox now. Daft Jamie is frightened of the dark, but he trusts the Doctor and follows him and Evelyn to the TARDIS. There, as he gazes in delight at his magical surroundings, the Doctor sets his ship in motion -- much to Evelyn’s confusion, as she was under the impression that it would be a bad thing to remove Daft Jamie from his proper place in history. However, the Doctor informs her that Knox’s meddling is already causing changes to history, and the only way they can stop him is by taking Jamie to 28 January 1829, and thus out of Knox’s time loop.

The TARDIS materialises back in the tunnels, but the Doctor prevents Evelyn from taking the frightened Jamie’s hand, doing so himself. He and Evelyn lead Jamie to the surface, where an angry mob has gathered to watch Burke’s execution. Aware that he can’t escape his fate, Burke puts on a show for the crowd, cursing them and praising himself. There’s no sign of Hare, who skipped the country after turning King’s Evidence; the Doctor assumes that Knox has set him up comfortably in another century, at least until he’s ready to bring him back to commit the same murders once more. As they watch the crowd, Daft Jamie is delighted to realise that the mob is shouting out his name; just as the Doctor had promised, he’s become famous. But Knox then arrives and callously tells Jamie that he’s famous because he’s dead; his body is wrapped in a sack in the surgery even as they speak. However, the Doctor then tells Jamie that Knox is the man who made him famous, and before Knox realises what he’s doing, the Doctor has prompted Daft Jamie to step forward and shake his hand. Like Knox, Daft Jamie doesn’t drink, and he is thus susceptible to the flu virus -- which he has now passed on to Knox. Too late, Knox realises that the Doctor tricked him into revealing his weakness and emerging from his time loop; he can’t rewind this action, and will remain infected even if he returns to the time loop now. All he can do is flee in his stolen TARDIS and try to find a cure elsewhere -- but now his alien clients and his viewing public will both be tracking him down for reneging on his promises. Enraged, Knox retreats to his TARDIS, vowing to find a cure and exact his revenge on the Doctor.