Publisher Summary This chapter discusses the virologic, immunologic, and epidemiologic aspects of immunosuppressive disease caused by type D retroviruses (SRV-1, SRV-2, MPMV) and by lentiviruses (SIV) in nonhuman primates. Insofar as AIDS is a human retroviral disease caused by HIV and the chimpanzee is still the only nonhuman species known to be susceptible to experimental infection with this virus, both of these other nonhuman primate models will be of great benefit, although they present a few limitations. HIV-2 appears to cause persistent infection in some macaques without inducing disease. This model may, therefore, help reduce the need for chimpanzees of African origin. Because SIV causes a persistent infection and fatal AIDS-like disease in Asian macaques, this system constitutes the most directly relevant animal model for human AIDS. Critical questions on retrovirus-induced immunopathology that can be assessed in these animal models which cannot be tested as directly for HIV include the role of cofactors for infection and disease, the viral determinants of pathogenesis, the significance of envelope gene variation, and the potential for protective immunization, both pre- and postexposure. Analyses of the effects of a variety of retroviruses in primates and nonhuman primates reveal the complexity of immunosuppression and prefigure a diversity of pathogenic mechanisms. New concepts learned in these systems will have fundamental implications on the understanding of viruses, the immune system, and regulation of gene expression, and may lead to the development of procedures to prevent or limit immunologic abnormalities caused by these viruses.