BACKGROUND: Youths perinatally infected with HIV often receive psychotropic medication and behavioral treatment for emotional and behavioral symptoms. We describe patterns of intervention for HIV-positive youth and youth in a control group in the United States. METHODS: Three hundred nineteen HIV-positive youth and 256 controls, aged 6 to 17 years, enrolled in the International Maternal Adolescent AIDS Clinical Trials 1055, a prospective, 2-year observational study of psychiatric symptoms. One hundred seventy-four youth in the control group were perinatally exposed to HIV, and 82 youth were uninfected children living in households with HIV-positive members. Youth and their primary caregivers completed Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-referenced symptom-rating scales. Children's medication and behavioral psychiatric intervention histories were collected at entry. We evaluated the association of past or current psychiatric treatment with HIV status, baseline symptoms, and impairment by using multiple logistic regression, controlling for potential confounders. RESULTS: HIV-positive youth and youth in the control group had a similar prevalence of psychiatric symptoms (61%) and impairment (14% to 15%). One hundred four (18%) participants received psychotropic medications (stimulants [14%], antidepressants [6%], and neuroleptic agents [4%]), and 127 (22%) received behavioral treatment. More HIV-positive youth than youth in the control group received psychotropic medication (23% vs 12%) and behavioral treatment (27% vs 17%). After adjusting for symptom class and confounders, HIV-positive children had twice the odds of children in the control group of having received stimulants and >4 times the odds of having received antidepressants. Caregiver-reported symptoms or impairment were associated with higher odds of intervention than reports by children alone. CONCLUSIONS: HIV-positive children are more likely to receive mental health interventions than control-group children. Pediatricians and caregivers should consider available mental health treatment options for all children living in families affected by HIV.