Lesions of the central nervous system were seen in 13/22 autopsies of Italian subjects affected by the acquired immune deficiency syndrome and including 19 intravenous drug addicts. Multinucleated cells similar to those originally described by Sharer et al. [1985] in response to direct central nervous system lesions by the human immune deficiency virus were seen in five subjects. Isolated or multiple opportunistic infections of the brain including cerebral toxoplasmosis (7 cases), progressive multifocal leukoencephalopathy (4), cytomegalovirus encephalitis (3), and tuberculous meningoencephalitis (2) were recognized. Finally, three cases of primitive cerebral lymphoma of large round cells were found. The central nervous system is a target, like the lymphoid tissue, of direct damage for the human immune deficiency virus, and it is frequently affected by opportunistic infections due to the immunological impairment sustained by the acquired immune deficiency syndrome.