We are reporting the cases of four children with a diagnosis of acquired immune deficiency syndrome (AIDS) who demonstrated a progressive encephalopathy manifested by loss of motor milestones or intellectual abilities, and weakness with pyramidal tract signs. Two patients were ataxic. One child was cortically blind and suffered myoclonic jerks before his death. Two of the patients had isolated seizures at some time during the disease course. Two patients developed secondary microcephaly and all four patients showed cortical atrophy on computed tomographic scanning. Three of the patients died. Postmortem neuropathological findings included gross cortical atrophy, microglial nodules, and intranuclear inclusions, as are described in the subacute encephalitis reported in adult AIDS patients. We propose that the possible pathogenetic mechanisms of this encephalopathy include opportunistic or persistent viral infection of the brain.