Immunophenotype analysis was used to characterize circulating lymphocyte subset levels in both rhesus monkeys that were chronically infected with SIVmac239 and in those that had resisted SIVmac239 infection as a result of prior vaccination with an attenuated SIV strain. Alterations in T, NK, and B cell subsets were compared with those previously identified in humans chronically infected with HIV [8-11, 14, 22]. The well-known decrease in CD4+ cell levels was observed in the SIVmac239-infected animals. However, these animals had relatively little activation of circulating CD8+ T cells as compared with uninfected monkeys. This contrasts with chronically HIV-infected humans who have substantial activation of circulating CD8+ cells as evidenced by elevated HLA-DR and CD38 antigen expression on CD8+ cells as well as substantially increased percentages and numbers of total CD8+ cells. NK cells of the SIVmac239-infected animals, on the other hand, demonstrated the same changes recently described in HIV-infected humans, i.e., a decrease in circulating percentages and a decreased amount of FcRIII (CD16). B cell percentages were markedly increased in the SIVmac239-infected animals, a finding also noted in some children with HIV infection but not in HIV-infected adults. SIV delta nef-vaccinated/SIVmac239-challenged animals showed none of the immune alterations found in the SIVmac239-infected monkeys, providing further confirmation of lack of SIV disease in these vaccinated animals.