On the surface, Max Carlyle (Wesley Snipes) has it all: a happy marriage, two healthy children and a successful career as a commercial director. Until one night while on a trip to New York City, a chance encounter leads to a passionate and uncharacteristic affair with a beautiful, seductive and very married woman named Karen (NASTASSJA KINSKI). Although each vows to forget the psycho-sexual ballet that has consumed these formerly faithful spouses, Max is plagued with memories of this scorching tryst. When he returns home, he slowly begins to withdraw from the people closest to him, as his wife (Ming-Na Wen) struggles to understand her changed husband, his new attitude, and the distance that has so quickly grown between them.

One year later, Max’s best friend, Charlie (Robert Downey Jr.) is hospitalized as he battles the last stages of AIDS. When Max returns to New York with Mimi to comfort his ailing friend, he finds himself face-to-face with Karen, who is married to Charlie’s conservative brother, Vernon (Kyle MacLACHLAN). Thrown together by fate, Max and Karen try to resist their mutual feelings, but ultimately they are forced to confront an undeniable truth … and the unsettling and unexpected consequences that erupt from a One Night Stand.