Roberta is a bored suburban housewife who is fascinated with a woman, Susan, she only knows about by reading messages to and from her in the personals section of the newspaper. This fascination reaches a peak when an ad with the headline "Desperately Seeking Susan" proposes a rendezvous. Roberta goes too, and in a series of events involving amnesia and mistaken identity, steps into Susan's life.

A shy and mute seamstress goes insane after being attacked and raped twice in one day. She wanders the New York streets at night in a sexy black dress with her attacker's gun strapped to her garter belt, blowing away any man who tries to pick her up.