Clinical evidence suggests that cellular immunity is involved in controlling human immunodeficiency virus–1 (HIV-1) replication. An animal model of acquired immune deficiency syndrome (AIDS), the simian immunodeficiency virus (SIV)–infected rhesus monkey, was used to show that virus replication is not controlled in monkeys depleted of CD8⁺ lymphocytes during primary SIV infection. Eliminating CD8⁺ lymphocytes from monkeys during chronic SIV infection resulted in a rapid and marked increase in viremia that was again suppressed coincident with the reappearance of SIV-specific CD8⁺ T cells. These results confirm the importance of cell-mediated immunity in controlling HIV-1 infection and support the exploration of vaccination approaches for preventing infection that will elicit these immune responses.