To address the possible role of replicative senescence in human immunodeficiency virus (HIV) infection, telomere length, telomerase activity, and in vitro replicative capacity were assessed in peripheral blood T cells from HIV⁺ and HIV⁻ donors. Genetic and age-specific effects on these parameters were controlled by studying HIV-discordant pairs of monozygotic twins. Telomere terminal restriction fragment (TRF) lengths from CD4⁺ T cells of HIV⁺ donors were significantly greater than those from HIV⁻ twins. In contrast, telomere lengths in CD8⁺ T cells from HIV⁺ donors were shorter than in HIV⁻ donors. The in vitro replicative capacity of CD4⁺ cells from HIV⁺ donors was equivalent to that of HIV⁻ donors in response to stimulation through T cell receptor CD3 and CD28. Little or no telomerase activity was detected in freshly isolated CD4⁺ or CD8⁺ lymphocytes from HIV⁺ or HIV⁻ donors, but was induced by in vitro stimulation of both HIV⁺ and HIV⁻ donor cells. These results suggest that HIV infection is associated with alterations in the population dynamics of both CD4⁺ and CD8⁺ T cells, but fail to provide evidence for clonal exhaustion or replicative senescence as a mechanism underlying the decline in CD4⁺ T cells of HIV-infected donors.