Victorian adventurer and sexologist Sir Richard Francis Burton (John Robinson), following an “unfortunate encounter” with the Fountain of Youth in 1892, is 170 years old and living in Toronto, Canada. Burton, now living and working as the chief taxidermist at a Museum of Natural History[disambiguation needed], is searching for a centerpiece display for an exhibit in his Hall of Contagion. He comes up with the idea of featuring AIDS and the Patient Zero hypothesis. Accepting the popular belief that Zero introduced the virus to North America, Burton sets out to collect video footage from those who knew Zero to support the hypothesis. When Zero’s doctor (Brenda Kamino), mother (Charlotte Boisjoli) and former airline colleague Mary (Dianne Heatherington), who is now with ACT UP, all refuse to demonize Zero, Burton manipulates the footage to make it appear as if they do and includes doctored photographs of Zero showing signs of Kaposi’s sarcoma. He presents this preliminary version to the press.
The ghost of Zero (Normand Fauteux) materializes at a local gay bathhouse. No one can see or hear him, until Zero runs into Burton while Burton is spying on Zero’s friend George. Zero realizes that Burton can see him, although Zero does not show up on Burton’s video camera. The two strike a deal; Zero agrees to help Burton with his Patient Zero exhibit if Burton finds a way to make Zero appear.
The two return to the museum where Burton makes a ridiculous attempt to seduce Zero to ensure his participation. Rejecting his advances, Zero examines some of the other exhibits (including displays on Typhoid Mary and the Tuskegee syphilis study) before finding an African green monkey, another suspected early AIDS vector. The monkey (Marla Lukofsky) angrily denounces Zero for scapegoating her just as he has been scapegoated. Zero turns to Burton and they make love.
Under pressure from his director and the exhibit’s drug manufacturer sponsor, Burton steals Zero’s medical records in hopes of discovering new information. Zero and Burton examine an old blood sample of Zero’s under a microscope and discover Miss HIV (Michael Callen), who points out that the original study that was used to label Patient Zero as the first person to bring HIV to North America did not prove any such thing, but instead helped prove that HIV was sexually transmitted, leading to the development of safer sex practices. Under this interpretation, Zero could be lauded as a hero for his candor in participating in that original study. As Burton ponders this, an unknown fluid squirts from the eye pieces of the microscope, drenching Zero and making him appear on video. He joyously declares his innocence on tape but the effect only lasts five minutes before he fades away again. Zero angrily accuses Burton of not caring for him at all and only wanting to use him for the exhibit, then storms out.
Burton fails to complete the revised Patient Zero exhibit before its scheduled opening date. The museum curator substitutes the original presentation instead over Burton’s protests, leading to a renewed rush of press scapegoating Zero. The night after the exhibit opens, Mary and other ACT UP members break into the Hall of Contagion and trash the exhibit. Zero returns and Burton explains that he tried to stop the exhibit. Zero forgives Burton but says he wants to disappear again completely. Zero merges with his disfigured video image and, smoking a cigarette inside the video, sets off the fire alarm. The sprinklers destroy the video player and Zero vanishes.
A major subplot involves George (Richardo Keens-Douglas), a French teacher and former intimate of Zero’s. George is losing his sight to cytomegalovirus and is taking a drug that is manufactured by a company that, as a member of ACT UP, George is protesting. George struggles through the film to resolve his conflicted feelings over this, his guilt over abandoning Zero during the final days of his illness and his fear that the same thing will happen to him.