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The creation of an improved vaccine for global measles control will require an understanding of the immune mechanisms of measles virus containment. To assess the role of CD8⁺ cytotoxic T lymphocytes in measles virus clearance, rhesus monkeys were depleted of CD8⁺ lymphocytes by monoclonal anti-CD8 antibody infusion and challenged with wild-type measles virus. The CD8⁺ lymphocyte-depleted animals exhibited a more extensive rash, higher viral loads at the peak of virus replication, and a longer duration of viremia than did the control antibody-treated animals. These findings indicate a central role for CD8⁺ lymphocytes in the control of measles virus infections and the importance of eliciting a cell-mediated immune response in new measles vaccine strategies.