Chimeric primate lentiviruses composed of SIV and HIV genes may allow the analysis of the role of these discrete HIV genes in viral pathogenesis in macaque monkeys. We have constructed a chimeric virus in which the env, rev, tat, and vpu genes of HIV-1 Lai replace the env, rev, and tat genes of the SIVmac239 genome. This virus, SHIVsbg, replicates efficiently in rhesus (Indian and Chinese subspecies) and cynomolgus monkeys with viral loads in PBMC and lymph nodes of up to one infected cell per 30 cells during the acute phase of the infection. Sera from all monkeys recognize specific HIV-1 glycoproteins. The onset of lymphadenopathy in all animals was concurrent with a depletion of CD4 lymphocytes in peripheral blood. The virulence of this SHIV for rhesus and cynomolgus monkeys therefore closely parallels that of HIV-1 for human in the acute phase of the infection. Changes in the env and vpu genes of a molecular clone of HIV-1 can now be analyzed after passage in nonhuman primate species as the SHIVsbg replicates efficiently. The SHIVsbg-macaque model is an important step in the development of a readily available animal model for HIV-1 vaccine studies.