A new cell proliferation analysis by flow cytometry was applied to the mitogen induced cultures of peripheral blood mononuclear cells (PBMC) from either normal, healthy donors or those individuals who are infected by human immunodeficiency virus, type 1 (HIV-1). While phytohemagglutinin (PHA) stimulation of normal PBMC (nPBMC) yielded propagation of both CD4 (nCD4) and CD8 (nCD8) T cell subsets, similar activation of PBMC from certain HIV-1-infected individuals (HIV-PBMC) produced active proliferation of CD8 (HIV-CD8) cells but varying degrees of CD4 (HIV-CD4) cell destruction. However, no measurable viral p24 antigen was produced extracellularly. On the other hand, when the purified HIV-CD4 cells were similarly activated, no such cell death was noted and high titer p24 was detected in the culture supernatants. Addition of exogenous IL-2 to either HIV-PBMC or HIV-CD4 cultures, did not alter either CD4 cell death or HIV-1 p24 production. Isolated HIV-CD8 killed not only HIV-CD4 but also nCD4, when co-cultured and less proliferative fractions of CD4 cell population was the more preferred targets of the HIV-CD8 CTL activity. The presence of anti-CD4 CTL activity was closely associated with high CD8, but not with CD4 counts, of the HIV+ patients.