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OBJECTIVE: To assess the relationship between HIV-associated psychotic symptoms (i.e., delusions, hallucinations) and demographic, psychopathological and medical variables by comparing patients with and without cerebral opportunistic infections or metabolic encephalopathy. DESIGN: Cross-sectional study. PATIENTS: 26 patients admitted to hospital with HIV and new-onset psychotic symptoms, defined according to DSM-III-R criteria. OUTCOME MEASURES: A semistructured psychiatric interview using the Psychopathology Assessment Scale (AMDP-4) of the Association for Methodology and Documentation in Psychiatry system. Comprehensive medical assessments, including laboratory tests and computed tomographic scans, were also performed. RESULTS: Patients with cerebral opportunistic infections or metabolic encephalopathy (i.e., "secondary" psychosis, n = 13) were more likely to show disorders of consciousness, disorders of orientation and disturbances of attention and memory than those with no evidence of HIV-related cerebral disease (i.e., "primary" psychosis, n = 13); 10 patients (77%) with cerebral opportunistic infections or metabolic encephalopathy and only 1 (8%) patient without (p < 0.001) were diagnosed with delirium. These associations were stronger for the "secondary" patients with no focal brain lesions than for those with lesions. CONCLUSIONS: These findings suggest that "organic" symptoms of psychosis in those infected with HIV are related to the systemic and cerebral complications of HIV infection rather than to the psychotic process itself.