Potent virus-specific cytotoxic T lymphocyte (CTL) responses elicited by candidate AIDS vaccines have been shown to provide short-term control of viral replication following pathogenic viral challenges in rhesus monkeys. We have recently shown that vaccines that control rather than prevent immunodeficiency virus infections are still subject to immune escape. In particular, viral mutations can develop that result in viral escape from recognition by immunodominant CTL, loss of immune control of viral replication, and clinical disease progression. These data suggest that viral escape from CTL may prove to be a significant limitation of the current generation of CTL-based AIDS vaccines.