After breaking up with her girlfriend, a nightclub singer, Jane (Whoopi Goldberg), answers a personal ad from Robin (Mary-Louise Parker), a real estate agent with AIDS, seeking a cross-country travel partner. On their journey from New York City to Los Angeles, the two stop by Pittsburgh to pick up Robin's friend Holly (Drew Barrymore), who is trying to escape an abusive relationship. With three distinct personalities, the women must overcome their differences to help one another.