BACKGROUND: Associations between abnormal body fat distribution and clinical variables are poorly understood in pediatric HIV disease. OBJECTIVE: Our objective was to compare total body fat and its distribution in perinatally HIV-infected and HIV-exposed but uninfected (HEU) children and to evaluate associations with clinical variables. DESIGN: In a cross-sectional analysis, children aged 7-16 y in the Pediatric HIV/AIDS Cohort Study underwent regionalized measurements of body fat via anthropometric methods and dual-energy X-ray absorptiometry. Multiple linear regression was used to evaluate body fat by HIV, with adjustment for age, Tanner stage, race, sex, and correlates of body fat in HIV-infected children. Percentage total body fat was compared with NHANES data. RESULTS: Males accounted for 47% of the 369 HIV-infected and 51% of the 176 HEU children. Compared with HEU children, HIV-infected children were older, were more frequently non-Hispanic black, more frequently had Tanner stage >/=3, and had lower mean height (-0.32 compared with 0.29), weight (0.13 compared with 0.70), and BMI (0.33 compared with 0.63) z scores. On average, HIV-infected children had a 5% lower percentage total body fat (TotF), a 2.8% lower percentage extremity fat (EF), a 1.4% higher percentage trunk fat (TF), and a 10% higher trunk-to-extremity fat ratio (TEFR) than did the HEU children and a lower TotF compared with NHANES data. Stavudine use was associated with lower EF and higher TF and TEFR. Non-nucleotide reverse transcriptase inhibitor use was associated with higher TotF and EF and lower TEFR. CONCLUSION: Although BMI and total body fat were significantly lower in the HIV-infected children than in the HEU children, body fat distribution in the HIV-infected children followed a pattern associated with cardiovascular disease risk and possibly related to specific antiretroviral drugs.