We examined psychiatric correlates of human immunodeficiency virus (HIV) infection in a major risk group for acquired immunodeficiency syndrome, men with hemophilia. A central goal was to identify psychosocial factors associated with increased vulnerability to psychiatric distress after infection with HIV. Seventy-five hemophiliacs, 31 of whom were HIV seropositive (HIV+), were studied. The HIV+ men had elevated depression, anxiety, and anger-hostility symptom scores relative to those of men who were seronegative for HIV. There were no additional symptom differences among men according to infection stage or clinical severity of hemophilia. Men with any of eight psychosocial characteristics were particularly susceptible to effects of infection on mental health: a personal history of psychiatric distress before HIV diagnosis; familial psychiatric history; a high school education or less; low social support from one's wife; low family support; low friend support; a poor sense of mastery over one's life; and experiencing recent life events involving loss. The HIV+ men with one or more such characteristics were highly symptomatic; remaining HIV+ men had significantly lower symptom levels, similar to the low levels noted in the men seronegative for HIV. The findings provide initial empiric support for the notion that clinical services to alleviate emotional distress should be targeted to intervene on HIV+ persons' psychosocial assets and liabilities.