In order to characterize the effects of HIV (human T-lymphotropic virus type III/lymphadenopathy-associated virus) on the immune system, Leu8^– and Leu8⁺ subsets of CD4 and CD8 cells were studied in seropositive homosexually active men without acquired immune deficiency syndrome (AIDS). Controls included both heterosexual men and HIV-seronegative homosexually active men. The decrease in CD4 levels, observed in HIV-seropositive men who were asymptomatic, as well as in those who had persistent generalized lymphadenopathy or constitutional symptoms of HIV infection, occurred proportionally in both the Leu8^– and the Leu8⁺ CD4 subsets. This observation, that HIV infection does not selectively diminish either subset of CD4 cells, indicates that the selective loss of T cell-mediated functions which accompanies the development of AIDS is not related to preferential loss of the Leu8⁺ CD4 subset. Among CD8 cells, however, HIV infection resulted in a threefold elevation in the number of Leu8^– CD8 cells, while the number of Leu8⁺ CD8 cells remained constant. The increase in Leu8^– CD8 cells was present in recent seroconverters, persistently seropositive men, and patients with AIDS. We propose that the increase in Leu8^– CD8 cells represents an HIV-specific cytotoxic T-cell response. These cells may operate by killing infected CD4 cells, thereby partially controlling viral infection while simultaneously contributing to the destruction of the immune system.