Simian immunodeficiency virus (SIV) gag-specific major histocompatibility complex (MHC)-restricted cytotoxic T-lymphocyte (CTL) activity was elicited in four out of six cynomolgus macaques after two immunizations with SIV gag recombinant vaccinia virus (rVV). No activity could be seen in three out of three non-immunized control animals. Low levels of anti-gag antibody were also seen in the same four responding animals. Virus-specific, MHC-restricted CTL are thought to give some protection and to assist in recovery in viral infection, and the induction of such CTL following vaccination with a single viral protein should act as an encouragement to those proposing similar vaccination studies in man.