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To compare the rates of psychopathology in youths perinatally infected with HIV (N = 319) with a comparison sample of peers (N = 256) either HIV-exposed or living in households with HIV-infected family members.Participants were randomly recruited from 29 sites in the United States and Puerto Rico and completed an extensive battery of measures including standardized DSM-IV-referenced ratings scales.The HIV+ group was relatively healthy (73% with CD4% >25%), and 92% were actively receiving antiretroviral therapy. Youths with HIV (17%) met symptom and impairment criteria for the following disorders: attention-deficit/hyperactivity disorder (12%), oppositional defiant disorder (5%), conduct disorder (1%), generalized anxiety disorder (2%), separation anxiety disorder (1%), depressive disorder (2%), or manic episode (1%). Many youths with HIV (27%) and peers (26%) were rated (either self- or caregiver report) as having psychiatric problems that interfered with academic or social functioning. With the exception of somatization disorder, the HIV+ group did not evidence higher rates or severity of psychopathology than peers, although rates for both groups were higher than the general population. Nevertheless, self-awareness of HIV infection in younger children was associated with more severe symptomatology, and youths with HIV had higher lifetime rates of special education (44 vs 32%), psychopharmacological (23 vs 12%), or behavioral (27 vs 17%) interventions. Youth-caregiver agreement was modest, and youths reported more impairment.HIV infection was not associated with differentially greater levels of current psychopathology; nevertheless, investigation of relations with developmental changes and specific illness parameters and treatments are ongoing.