A number of studies have established high human immunodeficiency virus (HIV) seroprevalence among severely mentally ill men and women living in large urban areas. Much less research has characterized the patterns of risk behavior that contribute to elevated vulnerability to HIV/AIDS among the mentally ill, as well as psychological, situational, and gender-related influences on risk in this population. One-hundred thirty-four severely mentally ill men and women who reported sexual activity outside of an exclusive relationship or with high-risk partners completed an extensive measure battery concerning HIV risk. Knowledge about HIV was low and sexual risk behavior levels were high in the sample. On average, condoms were used in only 32% of intercourse occasions in the past three months, and nearly one-half of participants reported multiple sexual partners in the same period. Patterns common in the sample were sex associated with substance use; coerced sex, bartering sex for money, food, clothes, or a place to stay; and sex with injection drug user partners. Factors predictive of greater risk were being female, presently being in a relationship, perceiving oneself to be at risk, high levels of alcohol use, and weak risk reduction behavioral intentions. Mental health programs serving severely mentally ill men and women are reaching a population at elevated risk for contracting HIV infection, and can serve as a venue for targeted HIV prevention interventions.