We investigated the long-term health effects of HIV-1 infection in homosexual men not close to developing AIDS by comparing 916 HIV-1-seropositive (SP) men at least 1.67-3.67 years prior to a clinical AIDS diagnosis to 2,161 HIV-1-seronegative (SN) controls. The SP group reported a higher total of 12 distinct symptoms (fatigue, shortness of breath, night sweats, rash, cough, diarrhea, headache, thrush, skin discoloration, fever, weight loss, and sore throat/mouth) than did the SN group (p < 0.0001), corresponding to at least 5.6 more days/year of such symptoms. The SP group had lower body mass index (p < 0.0001) and lower hemoglobin (p < 0.0001). The SP group was more depressed, as measured by CES-D score (p = 0.047), before knowledge of one's serostatus was likely, and became even further depressed (p = 0.038 for increase in depression) after the HIV-1 serostatus test was accessible to high-risk groups. These associations remained unchanged in multivariate models, incorporating other covariates.