Infection in humans with the lentivirus HIV-1 typically results in the development of a chronic disease state characterized by the slow decline of CD4+ lymphocytes, the development of immunosuppression, and the development of opportunistic infections, ultimately leading to death. Although the average course of disease runs approximately 10 years, shorter and longer progression times have been noted. These alterations are presumed to be, at least partially, a factor of viral variation. The simian immunodeficiency viruses (SIVs) are the nonhuman primate counterparts to HIV. Several of these isolates, including SIV from sooty mangabey monkeys, induce a remarkably similar disease in Asian macaques. Recently, variants of SIV from sooty mangabey monkeys and SIV from African green monkeys have been described, which are increasingly more pathogenic. As in HIV-1 infections, this is probably due to genetic variation. On the basis of these findings, atypical viruses with tremendous pathogenic potential can arise from apathogenic or moderately pathogenic viruses.