San Francisco, 1976. Carolyn McConnell, a pre-med student who dreams of finding a cure for cancer, stumbles across a vampire attack when she follows an interesting British girl out of a bar. Carolyn, not knowing whether to be excited or terrified, is swept along with the flow and follows the girl, Sam Jones, and her friend the Doctor. They track down the vampire Eva to her home, where the Doctor threatens to stake her unless she reveals where the other vampires are hiding. Eva struggles, and in the end Carolyn is uncertain whether the Doctor staked Eva or Eva staked herself. The Doctor and Sam depart, and the Doctor leaves Carolyn an n-dimensional hypercube with which she can contact him if she ever has more vampire trouble.
By 1997, Carolyn has become a medical researcher, and her boyfriend James Court, a theatrical lighting designer, has learned to tolerate her interest in vampires. When a prominent senator is found near a Goth bar named The Other Place with all of the blood drained from his body, Carolyn takes her collection of news clippings to the police, and is put in touch with General Kramer of UNIT. One of Kramer’s best officers was recently killed while investigating the senator’s death, and Kramer, needing help, asks Carolyn to act as her unofficial scientific advisor. James, unable to take their talk of vampires seriously, offers to speak with the owner of the Other Place, who happens to be a friend of his. He doesn’t return, and the terrified Carolyn assembles her hypercube and calls in the Doctor.
While the Doctor, Carolyn and Kramer plan their next move, Sam researches the statistics on unexpected deaths by blood loss, and meets a young doctor from an inner-city hospital. David Shackle, who seems to affect a world-weary tone to counter the hopelessness of his situation, informs her that two hundred homeless people have died over the last six months, and that nobody has noticed. He accompanies the Doctor, Sam, Carolyn and Kramer to the Other Place, where the Doctor tries to question its owner. He fails to learn anything, Shackle is mugged when he gets bored and starts questioning people, and Sam is attacked by an emaciated vampire on the club dancefloor. As Sam recovers in hospital, Kramer advises her to stop travelling with the Doctor, telling her she’s too young to throw herself into the front lines. Sam starts to wonder whether the Doctor deliberately let her get attacked to show her how dangerous travelling with him could be.
Shackle goes to his friend Joanna Harris for advice, but her brutally honest responses reinforce his growing conviction that life is meaningless. He is unaware that she is in fact the leader of the local vampire coven. The Doctor and Carolyn return to the Other Place and wait for a vampire to show up; the young and arrogant Slake eventually confronts them, but the Doctor informs Slake that he is a Time Lord and demands that he arrange a meeting with his leader. Cowed, Slake reports to Harris, who agrees to meet the Doctor at the disused Orpheum Theatre which the vampires have made their home. The Doctor agrees to her terms, but Kramer, against his wishes, calls in her UNIT troops and has them stand by for action.
As an act of good faith, Harris agrees to release James, who has been kept alive as a hostage. It is the Doctor’s duty as a Time Lord to wipe out the vampire, but he would prefer to find a peaceful solution; perhaps he can help Harris to develop an artificial food source so they don’t have to kill to survive. Harris admits that she’s been working along similar lines for some time, but she isn’t sure whether she can trust the Doctor. To ensure mutual co-operation they undergo a bloodfasting, establishing a psychic link which will cause each to suffer any injuries inflicted upon the other, up to and including death. Kramer is furious when she learns what the Doctor has done, but it’s too late now; in any case, the Doctor wants to avoid a major battle, as the Time Lords may decide to sterilise the entire city if they discover a vampire coven is present.
James flees, unable to deal with the existence of vampires, alien Time Lords and the fact that Carolyn doesn’t want to leave with him. Carolyn, feeling betrayed that he’s left her behind, decides to leave with the Doctor once the vampires are dealt with. In the meantime, she uses the resources of the TARDIS to study the “vampire factor” in their blood and try to design an artificial food source. Shackle, meanwhile, spends the night working on a 15-year-old gang member who dies of his gunshot wounds anyway, and when he goes to Harris for solace she has none to provide. Realizing that he is now exactly where she wants him, she reveals her true identity and offers to turn him into a vampire; she’s been working on him for some time, hoping to enlist his help in her project. Shackle goes to the Doctor for help, but even the Doctor’s love of life can’t shake him out of his depression. The Doctor orders Harris not to turn Shackle, but this just leaves Shackle alone and suicidally depressed, with nowhere to go.
Slake, who first agreed to become a vampire for the dark romance of it, is furious with Harris for trying to end the Hunt. He has been stirring up the young vampires with visions of a life beyond morality, and he’s the one who killed the senator and the UNIT agent, just for the excitement. Determined to provoke a war he’s certain he will win, he leads the younger vampires to the Other Place to kill everyone in the club. Harris and the Doctor get wind of the attack, and the Doctor shows up with undercover UNIT agents who evacuate the club while he distracts and upstages Slake. When Harris and the elder vampires arrive, Slake reluctantly backs down, but plans to ambush Harris at her medical centre and kill her for the humiliation. Instead, he finds the despairing Shackle, and, amused by his story, he turns him. He then learns that Harris and the Doctor are bloodfasted, and realizes that he only need kill one of them to be rid of both. Galvanised, he goes to the young vampires with another plan; take out the elder vampires one by one, and then go for either Harris or the Doctor.
Sam, still traumatised by the assault in the club, can’t understand why the Doctor is protecting the lives of multiple murderers, and is convinced that Harris has somehow brainwashed him. She follows Harris to a secret cellar laboratory elsewhere in the city, where she finds that Harris is keeping childlike, naked humans in cages, but before she can do anything about it, Harris finds and attacks her. The Doctor, meanwhile, has tracked down James and is trying to convince him that Carolyn’s acceptance of vampires is not a rejection of James. When Harris attacks Sam, however, the Doctor senses it through their bloodfasting and threatens to throw himself out of the window of James’ hotel room, eight stories up, to stop her. Harris, terrified and furious with the Doctor, throws Sam into a cage and then goes out to kill a homeless man just so the Doctor will experience it. Even though the Doctor now understands just how betrayed she felt by his turning the bloodfasting against her, he doesn’t regret doing it; when Sam hears him insisting he would do anything to save her, she realizes she was wrong about him. The caged humans turn out to be clones Harris has grown as an artificial food source, but the Doctor refuses to countenance the development of a race of “battery humans”; Harris must look elsewhere for a solution.
A dying elder vampire contacts Harris and warn her that the youngsters have killed them all, and the Doctor and Harris now have no choice; Slake has declared war, and they must fight back. Carolyn, using Harris’ notes and the resources of the TARDIS medical laboratory, has found a way to kill the vampires using a solution of silver nitrate and taxol, and the Doctor puts Sam and Harris to work mixing more of the solution. He, Carolyn and Kramer return to Carolyn’s home to plan their next move, but they are attacked by the vampires and must seek shelter with James. The Doctor, realizing that the vampires will have fled the theatre as it is now known to be their home, convinces James to help him set a trap for them there. Upon arriving at the theatre they are attacked by the vampire squirrels Slake has left behind as guards, and James saves the sleep-deprived Carolyn’s life when she reacts too slowly to the attack.
While forced to work alongside Harris, Sam admits that she’s never really had to fight to prove her beliefs; this is why she ran away with the Doctor and insists upon fighting alongside him. Slake and his cronies then attack the laboratory, along with the emaciated vampire who attacked Sam; Harris identifies him as “Weird Harold”, a vampire who went mad with hunger when he awoke from a healing coma to find that a building had been built over top of him in the intervening years. Sam, knowing the Doctor will die if Harris does, holds Weird Harold off while Harris escapes, and kills him with an injection of the vampire repellent. She is, however, captured by Slake, who contacts the Doctor and informs him that they have a hostage. The Doctor agrees to meet him at the Orpheum Theatre for a final confrontation.
With James’ help, the UNIT troops have set up a lighting grid to simulate the effect of sunlight, and when the vampires arrive they switch on -- but the sunlight effect isn’t exact enough, and doesn’t kill them. The Doctor gives himself up to the vampires to distract them from Sam, and they feed on him -- and die. The Doctor, apparently dying, asks Harris to turn him, but when she starts to drink his blood she realizes too late that he’d drunk a vial of the vampire repellent as a precaution before the other vampires even arrived. Harris dies, but the Doctor administers CPR and restores her to life; although the vampire factor in her cells has been destroyed, their bloodfasting has enabled her to survive as a human.
Kramer offers the stunned Harris a post as an unofficial consultant with UNIT, which could use a biologist with a thousand years’ experience. The Doctor and Sam depart as Carolyn returns to James, realizing that she needs his stability and love after all. What nobody knows yet is that Shackle, still unsure about his decision to become a vampire, hadn’t joined in the attack on the Doctor, and thus survived; now he’s alone in the theatre, the last of the vampires, wondering what to do next.