OBJECTIVE: The authors studied the lifetime, initial cross-sectional, and 6-month follow-up prevalence of mood disorders in asymptomatic HIV- infected and uninfected homosexual men who lived in an area with a low prevalence of HIV. They also determined the relationship between current major depression and potential depression risk factors. METHOD: Subjects included 98 asymptomatic HIV-infected and 71 uninfected homosexual men. Subjects underwent extensive clinical, psychiatric, neuropsychological, and laboratory evaluations. RESULTS: Similar proportions of HIV-infected and uninfected subjects reported a lifetime (29% and 45%, respectively), an initial current (8% and 3%), and a 6- month follow-up (9% and 11%) history of major depressive disorder. Anxiety disorders were less common, with similar proportions of HIV- infected and uninfected subjects reporting a lifetime (7% and 13%, respectively), an initial current (3% and 7%), and a 6-month follow-up (2% and 5%) history of anxiety disorders. There were no differences in the severity of mood symptoms between HIV-infected and uninfected subjects. Current major depression at initial visit was significantly associated with lifetime history of major depression but not with neuropsychological function or vitamin B12 level. CONCLUSIONS: These findings are in agreement with previous studies of areas with a high prevalence of HIV. However, the proportion of subjects with mood disorders is high compared with general population studies. Both HIV- infected and uninfected homosexual men may be at high risk for major depression, especially if they have a past history of depression. Moreover, in the asymptomatic stage of HIV infection, major depression does not appear to be secondary to HIV central nervous system effects or low vitamin B12 levels.