Immunologic changes in HIV-infected homosexual men without AIDS were studied using flow cytometry and monoclonal antibodies. A decline in CD4 cells occurred after anti-HIV antibodies detectable by ELISA developed. CD4 T-cell levels dropped to an average of 60% of their original level within 12-18 months after seroconversion. Subsequently, CD4 levels remained constant in most HIV seropositive men for several years. However, in men who developed AIDS, there was a rapid fall in the CD4 level during the 2 years prior to development of AIDS. Throughout the course of HIV disease, the total T-cell levels (CD3) remained constant, apparently due to CD8 lymphocytosis. The selective depletion by HIV infection of discrete functional subsets of CD4 cells was examined using 4B4, 2H4, HB-11, and Leu-8 monoclonal antibodies and dual color immunofluorescence. No selective depletion of CD4 subsets was noted using any of these reagents. However, selective activation of subsets of CD8 lymphocytes characterized disease progression. In particular, increases in the number of HLA-DR+, CD38+ (OKT10), and Leu-8- CD8 lymphocytes were associated with a fall in CD4 levels and development of AIDS.