Moses Herzog, an intellectually overstimulated 47-year-old professor of romantic literature, seems to be losing his mind over his recent divorce from young Madeleine Pontritter. Herzog lets his mind run wild with philosophy, spirituality, and childhood memories that bubble to the surface while he races around New York City, Martha's Vineyard, and Chicago, trying to regain his sanity and fight the inner hatred he feels threatening to consume him. After an arrest and release, Herzog retreats to his house in the countryside and completes his transformation. Healed from the past, he seems ready to begin anew.
Madeleine Pontritter hates and fears her ex-husband, Moses Herzog, and refuses to see him or let him see their daughter, June. She has begun a new life in Chicago with Valentine Gersbach, a married man who used to be her husband's best friend. Her story is told through Herzog's narration. Madeleine, known for being materialistic, ruthless, and shrewd, sets up Herzog to get the life she wants and to have Herzog foot a large part of the bill. Madeleine competes with Herzog for intellectual superiority and feels, in the end, she has defeated him.
Valentine Gersbach takes everything he can get from his best friend Moses Herzog, yet his motivation for doing so remains a mystery. Theatrical, likeable, and a bit of a dandy, Gersbach wins in life fairly easily. Herzog says Gersbach completely changes his personality when they meet because he is so enamored of Herzog. Eventually, it comes out Gersbach has been having an affair with Herzog's wife, Madeleine. In the end Gersbach remains triumphant. He is shown to be gentle, thoughtful, and capable of being June's stepfather.
Ramona Donsell wants Moses Herzog to be her steady boyfriend. In her late 30s she is ready for a serious relationship. Not to be fooled with, Ramona is intense, and she is excellent at sharing her feelings and communicating. Herzog trusts Ramona and feels comfortable sharing all of his woes with her. She intuits what Herzog needs to feel safe and acts on it without apology. Ramona's coolheaded logic and soothing social skills are just what Herzog needs. Ramona gets what she wants and knows how to keep it.