OBJECTIVE: Psychosis is an uncommon but serious complication of infection with HIV. This article presents the results of a study of HIV- infected individuals with psychosis. METHOD: The authors evaluated 20 HIV-infected men who had noniatrogenic new-onset psychosis without delirium, current substance abuse, or previous psychotic episodes. Clinical, neuropsychological, CSF, magnetic resonance imaging, and neuropathologic assessments were made. A comparison group consisting of 20 nonpsychotic HIV-infected men matched to the psychotic subjects with respect to age, race, years of education, and Centers for Disease Control HIV stage was also evaluated. RESULTS: The psychotic patients differed from the nonpsychotic comparison subjects in having significantly higher rates of past stimulant and sedative/hypnotic abuse or dependence and, at follow-up, a significantly higher rate of mortality. They also showed a trend toward greater global neuropsychological impairment. CONCLUSIONS: New-onset psychosis may be, at least in part, a manifestation of an HIV-associated encephalopathy.Abstract Teaser