Recent vaccine trials utilizing the simian immunodeficiency virus/macaque model of AIDS are beginning to yield clues regarding mechanisms of protective immunity. Although cytotoxic T lymphocyte responses to SIV may play a role in mediating protection against infection, protective immunity appears to correlate best with the development of antibodies able to neutralize primary or heterologous pathogenic viruses. Protection against disease or persistent infection may be achieved in the absence of sterilizing immunity, suggesting that new benchmarks for AIDS vaccines may be in order.