Background: With no cure or vaccine for AIDS expected in the near future, researchers have tried to locate predictors of high-risk sexual activity and develop interventions that emphasize primary prevention and encouragement of safe sex. This study examines the roles of depression, feelings of hopelessness, relationship status, and illness stage in mediating sexual activity among 85 HIV-seropositive (HIV+) gay men seeking psychiatric treatment for clinical depression. Method: Subjects were participants in a randomized, double-blind, placebo trial of imipramine. A self-report was used to assess sexual activity during the month prior to each assessment. Results: Before and after initiation of treatment, a substantial proportion of these men were sexually abstinent and the vast majority of those who were sexually active denied practicing unprotected anal intercourse. Sexual abstinence was found to be associated with feelings of hopelessness (t = 2.8, p <.01), diagnosis of AIDS (chi(2) = 11.3, p <.01), and lower CD4 count (t = -2.6, p =.01). Conclusion: The sexual activity of this sample was characterized by caution or abstinence rather than promiscuity and recklessness. Severity and alleviation of depression were not associated with sexual abstinence. The possible ramifications of sexual abstinence on the mental health and quality of life of HIV+ gay men are briefly discussed.