OBJECTIVE: Research shows that many chronic psychiatric patients are at risk for infection by the human immunodeficiency virus (HIV). This study investigated the effects of a behavioral skills training program designed to prevent HIV infection among chronic mentally ill adults living in an inner-city area. METHODS: Twenty-seven men and 25 women were randomly assigned either to a four-session AIDS prevention program emphasizing risk education, sexual assertiveness, condom use, risk- related behavioral self-management, and problem-solving skills or to a waiting-list group, who later received the same intervention. RESULTS: Compared with the waiting-list control group, participants in the prevention program demonstrated significant gains in AIDS-related knowledge and intentions to change risk behaviors. The prevention program also significantly reduced rates of unprotected sexual intercourse and increased the use of condoms over a one-month follow-up period. A subset of participants who provided two-month follow-up data maintained some behavior changes. CONCLUSIONS: A relatively brief, skills-focused AIDS prevention program for chronic psychiatric patients produced reductions in HIV risk behaviors. Such HIV risk reduction intervention programs may be of use in inpatient, outpatient, and community-based settings.