Primary infection of rhesus macaques with pathogenic strains of simian immunodeficiency virus (SIV) leads to rapid and dynamic changes in both viral load and T cell counts in the peripheral blood. We have performed a sequential analysis of peripheral blood CD4 and CD8 T cells in five macaques during the 8 weeks following SIVmac251 infection. We observed a transient lymphopenia of both CD4 and CD8 T cells during the first 2 weeks, followed by a rebound. The primary phase of infection was associated with changes in the T cells expressing CD25, CD69, or HLA‐DR and with a priming of the peripheral blood CD4 and CD8 T cells for a process of apoptosis in vitro that was enhanced by CD95 (Fas) ligation, and was detected in two macaques as early as 7 days after infection. Despite the small numbers of animals studied, the importance of the early transient CD4 and CD8 T lymphopenia was positively correlated with the viral load. No correlation was found, however, between the level of activation markers expressed or of priming for apoptosis in peripheral blood T cells and the viral load. Our findings suggest the possibility that the early activation and priming for apoptosis of CD4 and CD8 T cells may involve indirect, host‐related, mechanisms, or alternatively, that the T cells that remain in the peripheral blood during primary infection do not adequately reflect the viral‐mediated changes in T cell activation and death that may occur in the lymphoid organs throughout the body.