An effective acquired immunodeficiency syndrome (AIDS) vaccine should be capable of eliciting human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte (CTL) responses. We have explored the use of lentivirus-like particles produced in mammalian cells infected with a recombinant vaccinia virus to immunize for the induction of CTL in the simian immunodeficiency virus (SIV)/rhesus monkey model for AIDS. SIV-like particles in a threonyl-MDP-based adjuvant did not elicit a high frequency of SIV gag-specific effector cells in naive rhesus monkeys. However, immunization with these particles elicited a potent recall CTL response in monkeys previously vaccinated with a recombinant vaccinia-SIV virus. These observations suggest that poxvirus-produced virus-like particles may represent a safe immunogen for use in periodic boosting to maintain viable cell-mediated immunity to the AIDS virus.