OBJECTIVES To measure proinflammatory cytokines (PIC) in HIV-infected children beginning or changing antiretroviral therapy (ART), evaluating associations with virologic, immunologic, serum lipid, growth, and body composition measures, markers of growth hormone action and glucose metabolism. METHODS Forty-nine prepubertal HIV-infected children had measurements of viral load (VL), CD4 lymphocyte count and percentage, serum lipids, apolipoprotein AI/B, IGF-1, IGFBP-1, and IGFBP-3, anthropometry, bioelectrical impedance analysis, TNF-α, IL-1 β, and IL-6 at baseline and 48 weeks of ART. RESULTS Baseline levels were detectable (>0.1 pg/mL) for IL-1 β in 28 of 48, and for TNF-α and Il-6 in all 49 children. TNF-α decreased with ART (P < 0.001) and IL-6 demonstrated a similar trend (P = 0.065). Children with 48-week VL <400 copies/mL had greater declines in TNF-α (mean 45%) than subjects with higher VL (5%; P = 0.009). Each 10% improvement in CD4% was associated with 26% lower TNF-α (P = 0.002) and 31% lower IL-6 (P = 0.016). Greater reductions in TNF-α were associated with lower total/HDL cholesterol ratio (P = 0.003) at week 48. CONCLUSIONS In HIV-infected children initiating or changing ART, PIC were detectable at baseline and decreased over 48 weeks. Better immunologic responses were associated with greater reductions in TNF-α and IL-6. Reductions in TNF-α were associated with improved total/HDL cholesterol ratio.