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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.
In post-9/11 New York City, an eclectic group of citizens find their lives entangled, personally, romantically, and sexually, at Shortbus, an underground Brooklyn salon infamous for its blend of art, music, politics, and carnality.
Failed musician Jay abandoned his family and now earns a living as head bartender in a trendy London pub. Every Wednesday afternoon, a woman comes to his house for graphic, almost wordless, sex. One day, Jay follows her and learns about her. This eventually disrupts their relationship.