Many features of T-cell homeostasis in primates are still unclear, thus limiting our understanding of AIDS pathogenesis, in which T-cell homeostasis is lost. Here, we performed experiments of in vivo CD4⁺ or CD8⁺ lymphocyte depletion in 2 nonhuman primate species, rhesus macaques (RMs) and sooty mangabeys (SMs). Whereas RMs develop AIDS after infection with simian immunodeficiency virus (SIV), SIV-infected SMs are typically AIDS-resistant. We found that, in both species, most CD4⁺ or CD8⁺ T cells in blood and lymph nodes were depleted after treatment with their respective antibodies. These CD4⁺ and CD8⁺ lymphocyte depletions were followed by a largely lineage-specific CD4⁺ and CD8⁺ T-cell proliferation, involving mainly memory T cells, which correlated with interleukin-7 plasma levels. Interestingly, SMs showed a faster repopulation of naive CD4⁺ T cells than RMs. In addition, in both species CD8⁺ T-cell repopulation was faster than that of CD4⁺ T cells, with CD8⁺ T cells reconstituting a normal pool within 60 days and CD4⁺ T cells remaining below baseline levels up to day 180 after depletion. While this study revealed subtle differences in CD4⁺ T-cell repopulation in an AIDS-sensitive versus an AIDS-resistant species, such differences may have particular relevance in the presence of active SIV repli cation, where CD4⁺ T-cell destruction is chronic.