New York City, 1985. Prior Walter announces to his boyfriend Louis Ironson that he has been diagnosed with AIDS. Unable to cope with this, Louis leaves. This abandonment leaves Prior shattered. At the same time, Roy Cohn, a powerful lawyer and a right-wing political conservative is diagnosed with AIDS but demands that his doctor say that he has liver cancer as he does not want his homosexuality known in the circles he moves in. Cohn grooms his assistant, the milquetoast Mormon lawyer Joe Pitt, to go to Washington in order to protect him from a disbarment trial. At the same time Joe's wife Harper has become deeply unhappy and addicted to valium over the fact that Joe does not seem to want her sexually. Joe finally comes out and admits that he is fighting homosexual desires. When he calls to tell his mother that he is gay, she sells up everything she has in Salt Lake City and rushes to New York to help, but Joe has vanished - in fact has met and taken up with Louis. As he becomes increasingly more ill, Prior receives visitations from a female angel who has sex with him and then implants a holy book inside his body, telling him that he is a prophet and must sound the warning that human progress be stopped. And as Cohn falls ill in hospital, the ghost of the Communist spy Ethel Rosenberg, whom he helped convict and execute, comes to gloat at his nearing death.