We reviewed the neuropathologic characteristics of 52 cases of acquired immune deficiency syndrome (AIDS) at autopsy. Histologically significant neuropathologic lesions were found in 38 cases. We believed that infection was the predominant pathologic process in 26 cases; occasionally, multiple infectious agents were present. This included Toxoplasma encephalitis (n = 16), fungal abscess (n = 1), tuberculous abscess (n = 1), progressive multifocal leukoencephalopathy (n = 2), cysticercosis (n = 1), and Escherichia coli meningoencephalitis (n = 1). Microglial nodules or perivascular inflammation suggested that encephalitis was the most likely cause in five cases. In two additional cases, a primary demyelinating process that was apparently related to cytomegalovirus was present. Vascular or hypoxic diseases were present in nine cases. The findings included intracerebral hemorrhage (n = 1), subarachnoid hemorrhage (n = 2), infarction (n = 2), diffuse hypoxic changes (n = 5), cerebral edema (n = 1), and rare thromboemboli with extravasation of RBCs (n = 1). One case of primary lymphoma was observed. The CNS lesions were the proximate cause of death in 15 patients. The CNS complications of AIDS are varied and often are the major manifestation of the syndrome.