The host immune system is profoundly affected during the acute phase of progressive immunodeficiency lentiviral infections. Studies of these alterations have been quite restricted in humans because of the limited availability of samples from acutely HIV-infected persons. Therefore, numerous studies have turned attention to nonhuman primate models. Specifically, SIV-infected rhesus macaques (RMs) have been informative for understanding the pathogenesis of HIV infection in humans. Indeed, advantages of the nonhuman primate model include the ability to study the very early events after infection and the ability to retrieve copious amounts of tissues. In addition, nonhuman primates allow for comparative studies between non-natural and natural hosts for SIV, in which SIV infection results in progression, or not, to AIDS, respectively. Although SIV infection of RM is the best model for HIV infection, the immunologic and/or virologic phenomena in SIV-infected RM do not always reflect those seen in HIV-infected humans. Here virologic and immunologic aspects of acute HIV infection of humans and SIV infection of Asian and African nonhuman primates are discussed and compared in relation to how these aspects relate to disease progression.