The simian immunodeficiency virus model provides an effective system in which to answer questions about the mechanisms of pathogenesis of primate lentiviruses. The strength of an animal model is that defined virus strains and molecular clones can be examined for the role they play in the pathogenesis of disease; that both viral and host factors can be examined throughout infection; and that drugs can be tested for their efficacy in preventing virus replication and the expression of disease. Use of an animal model is essential to answer questions that are either difficult or impossible to examine in humans infected with HIV. Studies of the pathogenesis of central nervous system disease in HIV-infected individuals are complicated by the variability in the time course and manifestations of disease, the great variety of infecting viruses, the inability to examine the affected organs throughout the course of disease and the variable effects of drug therapy on disease progression. In addition, animal models are crucial for vaccine development and testing.