SIR-Infection of macaques by simian immunodeficiency viruses (SIV) leads to a disease similar to that produced by HIV in man. This simian system is widely used in the United States and Europe as a model for the development of vaccines against AIDS. There are several reports1-4 that inactivated vaccines completely protect against intravenous challenge with homologous SIV. It is widely assumed that, as with other viral vaccines, protection is mediated by immune responses to viral antigens in these vaccines. But, although the vaccines do induce high titres of antibodies to SIV, our attempts to correlate protection with titres of virus-neutralizing antibody or, indeed, any anti-SIV antibodies (T. Corcoran et al. and PS et al., in preparation) have been uniformly unsuccessful. Similar observations have been reported by others1• 3• 5 and were discussed in News and Views6. We have demonstrated that inactivated purified virions or fixed SIV-infected cells are protective. During experiments to define the protective components in these vaccines and the minimum dose schedule, four macaques