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Brandon, a thirty-something man living in New York, eludes intimacy with women but feeds his deepest desires with a compulsive addiction to sex. When his younger sister temporarily moves into his apartment, stirring up bitter memories of their shared painful past, Brandon's life, like his fragile mind, gets out of control.

Restless and unhappy, two couples get caught up in infidelity and deception. Barry is a sullen businessman married to Mary, a writer who is unsatisfied with their relationship. Mary begins an affair with Jerry, a smug theater professor and husband of her friend, Terri, who is also a writer. Adding to the adulterous mix are Cary, a callous doctor, and Cheri, an art-gallery assistant.

A girl, Carola, whose vacation in Kenya takes an interesting turn when she becomes infatuated with a Masai. Carola decides to leave her boyfriend to stay with her lover. There, she has to adapt to the Masai's way of life and get used to their food which includes milk mixed with blood. She also has to face her husband's attitude towards women and what he expects from a wife. Nonetheless, Carola is welcomed warmly into the tribe she has chosen to join.

While traveling in Paris, author Henry Miller and his wife, June, meet Anais Nin, and sexual sparks fly as Nin starts an affair with the openly bisexual June. When June is forced to return to the U.S., she gives Nin her blessing to sleep with her husband. Then, when June returns to France, an unexpected, and sometimes contentious, threesome forms.

A man named Seligman finds a fainted wounded woman in an alley and he brings her home. She tells him that her name is Joe and that she is nymphomaniac. Joe tells her life and sexual experiences with hundreds of men since she was a young teenager while Seligman tells about his hobbies, such as fly fishing, reading about Fibonacci numbers or listening to organ music.

Two lifelong friends navigate complex sexual encounters and emotional entanglements, wrestling with societal norms and personal desires.