Infections involving the brain have become a major complication in patients with acquired immunodeficiency syndrome. We have reviewed 48 cases of central nervous system lesions in patients with acquired immunodeficiency syndrome. and its related complex. All patients had computed tomographic scans with contrast performed; 31 of 48 were intravenous drug abusers. Computed tomographic abnormalities found included 21 patients with multiple ring-enhancing lesions, 13 with single ring-enhancing lesions, 11 with single hypodense lesions, and three with multiple hypodense lesions. Twenty-five patients had a positive serologic reaction for Toxoplasma. Sixteen patients had brain tissues examined. Of the 16 patients, six had cerebral Toxoplasma (one with concomitant Mycobacterium tuberculosis), and ten had diagnoses other than toxoplasmosis (three of whom had a positive serologic reaction for Toxoplasma). Two patients had M tuberculosis; one patient had Nocardia asteroides with Salmonella enteritidis. Of the remaining seven patients, three had encephalitis of unknown cause, two had inconclusive tissue diagnoses, one had progressive multifocal leukoencephalopathy, and one had vasculitis. In the population of intravenous drug users, brain lesions from diseases other than toxoplasmosis may be just as prevalent. Attempts to obtain a diagnosis from brain tissue is highly recommended to permit the design of effective and specific therapy for those diseases amenable to therapy.