BACKGROUND Clinical reports from the United States indicate substantive mental health problems in perinatally human immunodeficiency virus (HIV)-infected youth that pose substantial barriers to optimizing their health. This pilot study explores rates and types of psychiatric and substance use disorders, as well as emotional and behavioral functioning in perinatally HIV-infected children and adolescents. METHODS Forty-seven perinatally-infected youths (9-16 years of age) and their primary caregivers recruited from a pediatric HIV clinic were interviewed using standardized assessments of youth psychiatric disorders and emotional and behavioral functioning, as well as measures of health and caregiver mental health. RESULTS According to either the caregiver or child report, 55% of youths met criteria for a psychiatric disorder. The most prevalent diagnoses were anxiety disorders (40%), attention deficit hyperactivity disorders (21%), conduct disorders (13%), and oppositional defiant disorders (11%). However, the majority of caregivers and children scored in the normative range on the symptom questionnaires on emotional and behavioral functioning. None of the demographic or child health variables or measures of caregiver mental health was significantly associated with presence of a child psychiatric disorder. There was an association between caregiver mental health and child emotional and behavioral functioning. CONCLUSIONS Standardized assessments of mental health identified very high rates of psychiatric disorders, primarily in the anxiety and behavioral domains, in this sample of youth with perinatal HIV infection. Mental health interventions should be integrated into medical care to help members of this highly vulnerable population optimize their health and well-being.