The objectives of this study were to investigate HIV-1 seroprevalence and risk factors, disease progression, and awareness of HIV-1 serostatus in a population of inner city, substance using, psychiatric inpatients. To pursue these goals, we tested 118 (103 M, 15 F) dually diagnosed, acute care inpatients for HIV-1 antibodies and administered structured interviews. Twenty-seven (23%, including 24 M and 3 F) of the subjects were HIV-1 seropositive. Seropositivity was twice as great among intravenous drug users and men who had sex with other men as among patients not belonging to either of these two groups. Logistic regression analysis among male subjects revealed a significantly elevated HIV-1 risk associated with a primary diagnosis of depression (odds ratio adjusted for age, race, and presence of an AIDS risk behavior = 4.2, 95% confidence interval = 1.1, 16.5;p= 0.04). Less than half of the seropositives knew their HIV-1 status prior to this study, one had AIDS and four had two or more constitutional symptoms of AIDS. The high rate of seropositivity in this indigent, dually diagnosed population presents challenges to the health-care community. That few individuals had HIV-1 related symptoms may have implications for other treatment settings.