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Although parents and caregivers may have primary responsibility for their children's medication- taking, surprisingly few studies have examined caregiver psychosocial correlates of children's adherence to antiretroviral therapy (ART). This cross-sectional, descriptive study examined the relationship between caregiver psychosocial characteristics and medication adherence among children with HIV. Fifty-four caregivers of children with HIV completed a demographic questionnaire, the Parenting Stress Index, the Brief Symptom Inventory, the Family Support Scale, and the Support Functions Scale. Adherence to ART was measured with children's 6-month pharmacy refill histories. Children and caregivers were primarily African American, urban, and poor (63% reported <$15,000 annual household income). Univariate analyses showed that an adherent classification (≥ 80% refill rate) was associated with shorter duration of highly active antiretroviral therapy (HAART) treatment, nondisclosure of the HIV diagnosis to the child, lower caregiver income level, having a nonbiologically related caregiver, and less caregiver psychiatric distress. In a multivariate logistic regression, duration of child's HAART treatment, child HIV disclosure status, caregiver income, and caregiver psychiatric distress accounted for 63% of the variance in adherence. Findings highlight the complexity of children's adherence to ART and the need for multicenter studies with greater sample sizes to explore in more detail the effects of caregiver psychological distress and child HIV disclosure status on adherence as well as the ways in which regimen fatigue and adherence fluctuate over time.