Prior Walter is diagnosed with AIDS that changes his life and he must deal with such new obstacle. Moreover, his partner abandoned him. He has also increasing hallucinations and Mormon's mother comes to New York in order to save her son's marriage. Meanwhile, Roy Cohn checks into the hospital.

Louis abandons a hospitalized Prior; Joe and Roy confide in each other over drinks. Later, Prior hears voices from his hospital bed while Louis solicits sex from strangers, and Joe makes a drunken confession to his mother.

Prior returns home and is visited by a pair of spectral namesake ancestors who herald the arrival of the messenger; a tussle with Joe leaves Roy with the ghost of Ethel Rosenberg. Later, Joe and Louis hook up in Central Park while Prior meets the angelic messenger.

The story continues with Prior finally confronting the visions, Cohn desperately trying to manipulate the system to his benefit - all the while haunted by one of his victims, and Harper attempting to regain control of her life.

Louis arranges a meeting with Prior; Joe visits Roy in the hospital and gets an unwelcome father's blessing; Prior drags Belize to the courthouse for a surprise meeting with the clerk and later strikes up a friendship with Hannah. High on morphine, Roy paints a different picture of heaven.

A fight with Joe leaves Louis badly scarred; Roy plays a final practical joke on Ethel; Prior wrestles the Angel and then addresses a review board in Heaven; Harper heads out West; Prior, outliving his diagnosis, pays a visit to his favorite angel and vows to keep living--free of secrets.