Prior is a white gay man in his early thirties living in New York. Coming from an ancient lineage of men named Prior Walter, his life is upended by a recent AIDS diagnosis. He possesses a sharp, sarcastic wit that he uses as a defense mechanism against his increasing physical vulnerability and isolation. When left alone, he begins hearing a mysterious voice that insists on his attention.

Louis is a Jewish gay man who works as a word processor in a Brooklyn courthouse. He is highly intellectual and prone to delivering long monologues about democracy, race, and politics. However, his philosophical outward persona masks a deep terror of sickness and an inability to handle emotional rawness, leading to severe tension in his personal life.

Joe is a young, conservative Mormon lawyer working as a chief clerk for a federal judge. He projects the image of an ideal Republican husband and strictly adheres to the rules of his religion. Beneath his polished exterior, he harbors intense conflict regarding his sexual orientation, often taking long, solitary walks at night to escape his domestic reality.

Harper is Joe's Mormon wife who rarely leaves their Brooklyn apartment. She manages her severe anxiety and feelings of isolation by taking Valium and slipping into vivid hallucinations. She is highly perceptive, intuitively sensing the truth about her husband's secrets even as she struggles to distinguish reality from her own imagination.

Roy is a highly influential, abrasive, and conservative New York lawyer. He boasts about his political clout and operates with very few moral boundaries. Upon receiving a devastating medical diagnosis, he aggressively denies the reality of his illness to protect his status, insisting instead that he has liver cancer.

Belize is a registered nurse and former drag queen working at a New York hospital. He is fiercely loyal, deeply compassionate, and possesses a sharp, no-nonsense wit. He acts as a primary caregiver and emotional anchor, providing blunt but necessary truths to those around him who refuse to face reality.

Hannah is Joe's strict, pragmatic Mormon mother who lives in Salt Lake City. She views the world through a rigid, uncompromising lens and reacts poorly to emotional vulnerability. When confronted with shocking news about her son, she responds with decisive action, immediately preparing to sell her home and travel to New York.

The Angel is a majestic, frightening supernatural entity who targets Prior. She represents a powerful, disruptive force that intrudes upon the physical world, bringing divine demands that challenge human progress and understanding.

An elderly, traditional Jewish rabbi who presides over the nursing home where Sarah Ironson lived. He views the world through the lens of history and migration, noting that the old generation of immigrants is slowly disappearing.

A hallucinatory travel agent created by Harper's Valium-influenced mind. He wears the uniform of the International Order of Travel Agents and provides a sounding board for Harper's deepest fears and her desire to escape her life.

Roy Cohn's long-time physician. He maintains a calm, professional demeanor even when faced with his patient's aggressive denial, attempting to give realistic medical advice despite Roy's threats.

The ghost of the historical figure executed for espionage. She returns to observe the man who illegally ensured her execution, watching his physical decline with a mixture of amusement and patience.

An ancestor of Prior Walter who died of the plague centuries ago. He is a blunt, historical figure who arrives to herald a supernatural messenger, expressing confusion at modern life and his descendant's lack of children.

A seventeenth-century aristocratic Londoner who also died of the plague. He assists in preparing the current Prior Walter for an impending supernatural visitation, adopting a slightly more refined tone than his predecessor.

A public relations official for the Reagan Justice Department. He is a pliable political operative who complies with Roy's demands and helps pressure Joe into accepting a government position.

A tough, practical real estate agent and friendly acquaintance of Hannah Pitt in Utah. She tries to convince Hannah not to make a sudden, rash move to New York, viewing the city as dangerous.

A pragmatic nurse who tends to Prior during his hospital stays and outpatient clinic visits. She maintains a professional distance but expresses sympathy for the devastating nature of the illness and the toll it takes on patients' loved ones.

Louis's recently deceased grandmother. She was a Jewish immigrant who carried her heritage across the ocean to America, building a family in a new country.