The immunopathogenesis of human immunodeficiency virus type 1 (HIV-1) infection has been associated with increased death by apoptosis of T cell subsets. In the present study, we have examined correlates of apoptosis of CD4⁺, CD8⁺CD28⁺, and CD8⁺CD28⁻ T cells in tonsillar lymphoid tissue in persons with HIV-1. Single-cell suspensions of tonsillar lymphocytes were analyzed by flow cytometry to determine the fraction of cells showing typical characteristics of apoptosis as well as the expression of activation markers within the live and the apoptotic cell populations. The proportion of cells carrying infectious provirus was quantified by limiting dilution analysis. Compared with uninfected controls, apoptosis of both CD4⁺ and CD8⁺ T cells was enhanced in HIV-1 infection and was higher among CD8+ than among CD4⁺ T cells. Apoptosis of CD28^- cells was more prevalent than apoptosis of CD28⁺ cells for both CD4⁺ and CD8⁺ T cells. Occurrence of apoptosis of CD4⁺ T cells correlated with provirus levels and proportional expression of the activation marker HLA-DR. Apoptosis of CD8⁺CD28⁺ cells correlated with expression of the activation markers CD69 and HLA-DR while apoptosis within CD8⁺CD28⁻ cells did not correlate with any of the studied parameters. Although apoptosis was much more prevalent among CD8⁺ than CD4⁺ T cells, CD8⁺ T cells still accumulated in tonsillar lymphoid tissue in persons with HIV-1. Our data may be interpreted to suggest that apoptosis of CD4⁺, CD8⁺CD28⁺, and CD8⁺CD28⁻ cells in tonsillar tissue is regulated by different mechanisms and the results are of importance to our understanding of the immunopathogenesis of HIV-1 infection.