Bellow's novel tells the story of Moses Elkanah Herzog, a scholar of Jewish heritage who is losing faith in himself. The novel opens shortly after his divorce from his second wife, Madeleine, who has taken up with his closest friend, Valentine Gersbach. Moses grows paranoid and is convinced that various figures in his life - his doctor, his lawyer, his therapist, and his aunt - conspired in the destruction of his marriage. He begins writing letters to friends, acquaintances, public figures and philosophers, none of which he sends, in a quest to make sense of his situation.
He spends the first half of the book in transit, first isolating himself in the country home he had bought for Madeleine, before fleeing to New York. There he meets up with his longtime lover, Ramona, but upon finding himself alarmingly susceptible to her charms, departs for Martha's Vineyard with a view of pursuing a less weighted affair in the sympathetic arms of Libbie, a recently married friend. As his ferry nears the port, Moses is overcome with guilt for taking advantage of Libbie's sympathy. He leaves after a short visit and returns to his bed in New York, discovering a letter from the babysitter of his and Madeleine's daughter, June. The letter tells of Valentine locking and abandoning tearful June in the car during a fight with Madeleine. Moses is outraged; the first hints of fatherly responsibility are revived in him.
The following morning, Moses writes more letters, bearing witness to Madeleine's abusive childhood and subsequently maniacal nature. We learn about Moses' cool, organized first wife, Daisy, and a little about his childhood in Montreal. Through writing letters, Moses seems to be rediscovering different parts of himself. He meets Ramona for dinner that night and finds himself overflowing with talk of his problems. Ramona eventually soothes him with sex, though Moses can never shut off his philosophizing brain.
After bidding Ramona goodbye the next morning, Moses elects to take charge of his fatherhood and fight for custody of June, determined to protect her from the seemingly abusive Valentine. He also resolves to reconnect with Marco, his son from his first marriage, after a long period of estrangement. He convinces his divorce lawyer, Simkin, to meet with him at the courthouse to discuss Junie's custody. Like almost everyone else in his life, Simkin alludes to Moses' mental instability. Eventually, however, he agrees. While waiting for Simkin at the courthouse, Moses is disturbed by a number of trials he witnesses, particularly one involving a mother accused of murdering her child. He experiences a painful flashback he has swallowed since his youth - of being raped on the street.
Alive with even more familial emotion, Moses travels to Chicago to visit the house of his ex-wife, Madeleine. On the way, he visits his father's old house and his widow, Taube, with whom he reminisces about his youth. Moses takes his father's old pistol, with which he himself was once threatened. He has a mind to kill Madeleine and Gersbach. He finds himself unable, however, to go through with it, having witnessed through the windows of Madeleine's home what a tender, gentle, loving stepfather Valentine is. He realizes that his father never meant to shoot him either and only meant to threaten him. He regains some faith in humanity.
He stays with a friend, Asphalter, to whom he addressed a letter earlier in the book and who was his informant on Madeleine's affair. Asphalter is in bereavement for his late monkey, whom he cherished. He describes for Moses the therapeutic effect of simulating one's own death and admitting to oneself the whole truth of what one feels for others. This warms Moses' heart. Asphalter arranges for Moses a meeting with his daughter to take place the next day.
Moses and June are enjoying a delightful outing when they suddenly get into a car crash. The police find Moses' unlicensed pistol and take him in for questioning. Madeleine comes by to pick up June and intimates Moses' dangerous insanity. Moses frightens her away. He is placed in jail until his brother, Will, comes to bail him out, whereupon he moves back out to the country house in Ludeyville. Here he writes and sends a few letters; for the first time in the novel, his voice is joyful. He resists his sibling's concerned urges for hospitalization, and instead sets about fixing up the house. He reunites with Ramona, and the novel ends as he is preparing dinner for her. He finally feels at this moment that he no longer needs to write. He is cured.
