The neuropathologic findings of brains and spinal cords removed at autopsy from 26 infants and children with AIDS is described; in two cases, only the spinal cords were available. The most common finding in the brains was dystrophic calcification of blood vessels of all calibers in the basal ganglia and deep cerebral white matter (21 og 24 cases). The next most frequent finding was subacute encephalitis (SE) (15 of 24 cases) with microglial nodules and multinulceated giant cells. Immunocytochemical and in situ hybridization studies showed HIV antigen or genetic sequences only in the brains of cases with SE. Multinucleated giants cells (MGC) were the most frequent cells with reaction products. MGC were labeled with ricinus lectin (RCA), but not with leukocyte common antigen (LCA) or glial fibrillary acidic protein. Many cells in microglial nodules were labeled with RCA, but not LCA; cells in the perivascular compartment were labeled with LCA, but not RCA. Corticospinal tract degeneration was noted in 15 of 20 spinal cords. In six cases tract degeneration was consistent with delayed myelination, and the remaining cases had axonal injury consistent with Wallerian degeneration. Opportunistic infections were rare (three cases). Central nervous system lymphoma occurred in three children and was the most common mass lesion. In two cases lymphoma occurred in the setting of a systemic polyclonal immunoproliferation possibly related to Epstein-Barr virus infection. Cerebrovascular accidents were noted in seven cases. Two cases had hemorrhage associated with immune thrombocytopenia; one hemorrhage was catastrophic. Two children had large vessel arteriopathy with multiple encephalomalacias. Two children had a necrotizing encephalopathy with encephalomalacia and vascular changes suggestive of a mitochondrial cytopathy.(ABSTRACT TRUNCATED AT 250 WORDS)