The long-term effects of HIV infection were evaluated by comparing data from two visits a mean of 18 months apart in groups of 148 persistently seropositive and 287 persistently seronegative homosexual men. At each visit, the seropositive men exhibited lower CD4 counts, CD4/CD8 ratios, hemoglobin concentrations and lymphocyte counts, and higher C1q binding, IgG and IgA levels. More important, the decline of the CD4/CD8 ratio and the rise of the C1q binding, IgG and IgA, progressed significantly in the seropositive group between visits. Seropositive men were at elevated risk of developing constitutional symptoms and generalized lymphadenopathy. An association was present between development of symptoms and inversion of the CD4/CD8 ratio. The 11 seropositive men who have progressed to AIDS had lower CD4 counts and CD4/CD8 ratios, and higher C1q binding, IgG and IgA, than 134 seropositive AIDS-free men a mean of 21.4 months prior to diagnosis. The AIDS group demonstrated greater decline between visits in the CD4 count, hemoglobin and white blood count (WBC) than the seropositive AIDS-free group. The present data document the long-term effects of HIV infection in a seropositive cohort and suggest the possibility of a subgroup particularly susceptible to the progressive effects of HIV that precede the development of the acquired immunodeficiency syndrome (AIDS).