As part of a larger study to characterize immune alterations in blood donors seropositive for human immunodeficiency virus (HIV), we measured subsets of CD4 (T helper/inducer) and CD8 (T suppressor/cytotoxic) cells by 2-color cytofluorometry. Alterations observed in asymptomatic seropositive donors (ASP) included: 1) decreased mean levels of Leu 8+ CD4 cells, although the proportion of Leu 8+ cells within the CD4 population was unchanged; 2) a selective increase in Leu 8- CD8 and Leu 18- CD8 cell levels; and 3) increased levels of both CD8 subsets defined by Leu 7, Leu 17, or HLA-DR expression. Alterations observed in symptomatic seropositive donors (SSP) were: 1) a further decrease in Leu 8+ CD4 cell levels, with a decrease in the proportion of Leu 8+ CD4 cells; 2) decreased levels of both Leu 18- and Leu 18+ CD4 subsets; 3) selective increases in Leu 8- and Leu 18- CD8 cell levels; and 4) increases in Leu 7+ CD8, Leu 17+ CD8, and HLA-DR+ CD8 subsets but not the reciprocal negative CD8 subsets. Thus, changes merely reflective of HIV infection included decreased levels of Leu 8+ CD4 cells and increased levels of Leu 8- CD8, Leu 18- CD8, Leu 7+ CD8, Leu 17+ CD8, and HLA-DR+ CD8 cells. Development of symptoms were associated with a further, preferential loss of Leu 8+ CD4 cells, proportional losses of both CD4 subsets defined by Leu 18 expression, and a return to normal levels of Leu 7- CD8, Leu 17- CD8, and HLA-DR- CD8 cells.