Neuropathological changes were studied in a consecutive autopsy series of 135 cases, comprising 73% of all patients who died of AIDS in Switzerland between April 1981 and December 1987. Central nervous system involvement was found in 119 patients (88%), 19 of which had multiple concomitant intracerebral lesions. Among the non-viral opportunistic infections, encephalitis due to Toxoplasma gondii was most frequent and occurred in 35 patients (26%), followed by central nervous system infection with Cryptococcus neoformans, which was found in five patients (4%). Cytomegalovirus (CMV) encephalitis was present in 14 patients (10%). Disseminated microglial nodules without morphological or immunocytochemical evidence of CMV was encountered in 18 patients (13%). However, in all but two of these patients there was evidence of extracerebral CMV infection, suggesting that CMV was responsible for these nodular encephalitides. Nine patients (7%) had progressive multifocal leukoencephalopathy (PML); in five of these, demyelination was associated with extensive tissue destruction and cyst formation. HIV-associated encephalopathy was observed in 21 patients (16%) and showed two characteristic morphological patterns: progressive diffuse leukoencephalopathy (PDL) and multifocal giant cell encephalitis (MGCE). PDL was observed in 13 cases and characterized by diffuse pallor and gliosis of the cerebral and cerebellar white matter with scattered multinucleated giant cells, but without significant inflammatory response. MGCE was found in eight patients and characterized by clusters of numerous multinucleated giant cells, rod cells, macrophages, lymphocytic infiltrates and occasional necroses. In our view, PDL and MGCE represent the two opposite variants of HIV-induced encephalopathies, with overlapping intermediate manifestations.