Declining blood CD4+ T-cell counts mark the progress of simian immunodeficiency virus (SIV) disease in macaques and model the consequences of untreated human immunodeficiency virus infection in humans. However, blood lymphocytes are only a fraction of the recirculating lymphocyte pool, and their numbers are affected by cell synthesis, cell depletion, and distribution among blood and lymphoid tissue compartments. Asymptomatic, SIV-infected macaques maintained constant and nearly normal numbers of recirculating lymphocytes despite the decline in CD4+ T-cell counts. Substantial depletion was detected only when blood CD4+T-cell counts fell below 300/μl. In asymptomatic animals, changes in CD4+ T-cell distribution were more important than lymphocyte depletion for controlling the blood cell levels.