Objective: Recombinant human growth hormone (rHGH) has been shown to increase mortality in adult trauma patients; however, little has been reported on its side effects in children. The acute phase response has been suggested to he a contributing factor to trauma mortality. Therefore, the purpose of this study was to examine the effects of exogenous rHGH on the acute phase response in pediatric burn patients. Design: Prospective, randomized, double-blind study. Setting: Shriners Hospital for Children. Patients: Thermally injured pediatric patients, ranging in age from 0.1 to 16 yrs. Interventions: Twenty-eight thermally injured children received either 0.2 mg/kg/day of rHGH or saline (placebo) within 3 days of admission and for at least 25 days. Measurements and Main Results: Measurements were patient demographics, incidence of sepsis, inhalation injury, mortality, serum constitutive proteins, acute phase proteins, proinflammatory cytokines and insulin-like growth factor-I (IGF-l), insulin-like growth factor binding protein (IGFBP)-1, and IGFBP-3. No differences could be demonstrated in age, gender, burn size, incidence in sepsis (20% vs. 26%), inhalation injury (46% vs. 27%), or mortality (8% vs. 7%) between those receiving rHGH or placebo. Serum IGF-l and IGFBP-3 increased with rHGH treatment, whereas serum IGFBP-1 decreased compared with placebo (p < .05), Burned children treated with rHGH required significantly less albumin substitution to maintain normal levels compared with placebo (p < .05). Those receiving rHGH demonstrated a decrease in serum C-reactive protein and serum amyloid-A and an increase in serum retinol-binding protein compared with placebo (p < .05). rHGH decreased serum tumor necrosis factor-alpha and interleukin (IL)-1 beta, whereas no changes were found for serum IL-1 alpha, IL-6, and IL-10 compared with placebo (p <.05). Free fatty acids were elevated in burned children who received rHGH (p < .05). Conclusion: Data indicate that rHGH does not increase mortality. rHGH decreased acute phase proteins, tumor necrosis factor-alpha, and IL-1 beta, which is associated with increases in constitutive hepatic proteins and IGF-l.