The relationship between cell-associated infectious human immunodeficiency virus type 1 (HIV) load (infectious units/10(6) peripheral blood mononuclear cells [IUPM]) and phenotypes of CD4+ and CD8+ lymphocytes was studied. IUPM were measured in 242 HIV-infected homosexual men by quantitative microculture and T cell subsets by two-color flow cytometry. In multivariate analysis, IUPM correlated negatively with CD4+ lymphocyte level and with a diagnosis of AIDS and positively with the proportion of CD8+ lymphocytes expressing the activation marker CD38. After adjusting for level of CD4+ lymphocytes, men with AIDS had significantly lower IUPM than those without AIDS. The correlation between IUPM and CD4+ lymphocyte level was largely explained by correlation with level of CD4+ lymphocytes with resting phenotypes (HLA-DR-, CD38-) rather than with those expressing HLA-DR and CD38. Thus, subsets of CD4+ lymphocytes may vary in cell-associated infectious HIV content at different stages of HIV infection.