Simian immunodeficiency virus (SIV) infection of macaques is the best available animal model for studying the pathogenesis of AIDS. Experimental inoculation of macaques with SIV results in a persistent infection that leads to immunodeficiency, opportunistic infections, and death. Most aspects of the illness, including immunologic and virologic parameters, are easily quantified. Furthermore, pathologic processes can be evaluated throughout the course of experimental infection. Recently, molecular clones of SIV proviral DNA have been used to study genetic variation and specific viral determinants of pathogenesis. Considered together, these observations support the continued detailed study of SIV infection of macaques as a model for human AIDS.