An increasing body of evidence suggests that a vaccine that elicits anti-HIV-1 cellular immunity could provide the basis for an effective AIDS vaccine. Comparative immunization experiments testing a variety of vaccine approaches have demonstrated that replication-incompetent adenovirus vectors are an effective means for eliciting cytotoxic T-lymphocyte (CTL) immune responses against HIV-1 antigens. These immune responses effectively control viremia in nonhuman primates following challenge with simian AIDS viruses. Such data, coupled with epidemiology studies that identify HIV-1 gag, pol, and nef as the best antigens for broadly directed cellular immune responses, provide guidance for the development of a potential AIDS vaccine.