Lack of information on the mechanisms of protective immunity to AIDS virus infection represents a major obstacle to the development of a rational strategy for an effective HIV vaccine. In macaques, immunization with live attenuated simian immunodeficiency viruses has induced the most potent protective immunity and continued study promises a better understanding of the nature of protective immune responses. Recent evidence supports involvement of both cytotoxic T lymphocytes and neutralizing antibodies in protective immunity against infection by simian immunodeficiency virus, but more detailed studies are needed to document their relative importance.