Barney Mayerson wakes up in New York City lying next to his new assistant, Roni Fugate, not knowing where he is. His suitcase-sized, computerized psychiatrist, Dr. Smile, explains that he and Roni work as precogs for P. P. Layouts, a company owned by Leo Bulero. Their job is to predict what items will become popular in the near future for the Perky Pat sets. These sets are miniature layouts that the Mars colonists “enter” after ingesting the hallucinogenic drug Can-D, also sold by Bulero’s company. Can-D allows the ingester to access the imaginary suburban world of Perky Pat and Walter, her boyfriend. This world is realized in the Perky Pat layouts through miniature houses, cars, clothes, appliances, and whatever else P. P. Layouts deems appropriate to the suburban lifestyle.
Bulero finds out that rival entrepreneur Palmer Eldritch has just returned from Proxima Centauri with a hallucinogenic alien lichen that will threaten Can-D’s monopoly. Bulero tries to have Eldritch’s Chew-Z outlawed on the grounds that it is harmful, but when he is unsuccessful, he decides to kill Eldritch. His mission leads him first to the hospital on Jupiter’s moon, Ganymede, where Eldritch is reputed to be recuperating. Bulero finally catches up with Eldritch at his “demesne” on the Moon, where he finds himself ensnared in the shifting, nested realities of Chew-Z.
In the melee that ensues, the inhabitants of the hovels on Mars become the unwilling pawns in a war between the two entrepreneurs vying for dominance of the solar system. Meanwhile, Mayerson has immigrated to Mars, despite Dr. Smile’s assessment of him as too neurotic to immigrate. He comes face to face with the enigmatic Eldritch and thereby comes to terms with his own failures. By the end of the novel, the reader comes to realize that everyone, even Bulero, has entered Eldritch’s reality. All the characters are seen to take on Eldritch’s physical traits—mechanical eyes, steel teeth, and a prosthetic right arm—the three “stigmata” of the title.