Sooty mangabeys (Cercocebus atys) showed age-dependent changes in T cell regeneration. Younger animals had a high percentage of CD4+ CD45RA + T cells and a high concentration of T cell receptor excisional circles (TRECs) in peripheral blood, which indicated active thymopoiesis. In contrast, older animals had an increased T cell turnover, which suggested that most T cell production occurred in the periphery. In addition, the number of peripheral CD4+ T cells naturally decreased with age. Non-pathogenic SIVsm infection did not significantly change the T cell proliferation rate or the TREC concentration, though it did cause a moderate loss of peripheral CD4 + T cells. The viral load correlated negatively with age, which could be accounted for by the reduced availability of CD4 + target cells in older mangabeys. Thus, the number of susceptible target cells may be a limiting factor in natural SIV infection.