This review attempts to assess critically the literature on the neuropathology of acquired immunodeficiency syndrome in light of our experience with 172 patients with acquired immunodeficiency syndrome who underwent extensive postmortem examinations of the central and peripheral nervous systems. The neuropathologic manifestations of the disease can be divided into three categories: (1) primary or putative/indirect effects of the human immunodeficiency virus, (2) opportunistic infections, and (3) neoplasms. We discuss the known etiologic agents and postulated pathogenetic mechanisms responsible for the broad range of neurologic diseases observed in patients with acquired immunodeficiency syndrome.