Polymerase chain reaction (PCR) identified regions of the gag, LTR, and env genes of human immunodeficiency virus type 1 (HIV-1) in 5 (13%) of 38 high-risk homosexual men who were negative for HIV-1 antibodies by Western blot (WB). Significant increases in CD8+ cells, particularly those bearing activation CD8+CD38+ and CD8+Ia+ antigens, and marked reductions in CD4+ cells were detected in WB-PCR+ subjects compared with 33 WB-PCR- homosexuals. WB-PCR+ subjects had impaired B cell but not T cell functions. Immunologic characteristics of WB-PCR+ homosexuals were indistinguishable from those of 17 WB+PCR+ subjects. Subjects progressing from WB-PCR- to WB-PCR+ to WB+PCR+ showed sequential phenotypic and functional alterations in their B and T cell compartments. These changes and the presence of HIV-1 genomic sequences were the first indications of HIV-1 infection and together with p24 antigenemia signified an inevitable progression to AIDS.