Propranolol, a non-selective -blocker has been shown effective in hypermetabolic burn patients by decreasing cardiac work, protein catabolism and lipolysis. This study investigates the effect of propranolol on gene and protein expression changes in skeletal muscle of burned children using high-density oligonucleotide arrays to establish the genetic profiles and stable isotope technique to quantitate protein synthesis. Methods: Thirty-seven children (mean age 9.7 ± 1.1 years) were randomized into groups to receive placebo (n=23) or propranolol (n=14) titrated to reduce heart rate by 15%. Children had a greater than 40% total body surface area burns (mean 43 ± 5.6%). Protein net balance was determined by stable isotope infusion technique. Total RNA from muscle biopsies was isolated, labeled, and cRNA hybridized to the HG-U95Av2 Affymetrix array. Results: The mean net balance of protein synthesis and breakdown was minus 14.3 ± 12.9 nmol/min/100ml leg volume for placebo and plus 69.3 ± 130.7 nmol/min/100ml leg volume in the propranolol treated children, P=0.039. Comparison of 12,000 genes in burned children receiving placebo showed increased expression of two genes with time, while children receiving propranolol showed increased expression of 9 genes with a decrease in 5 genes. Conclusion: Burned children receiving propranolol showed a significant up regulation in genes involved in muscle metabolism and down regulation of an important enzyme involved in gluconeogenesis and insulin resistance compared to burned children receiving placebo. The upregulation of genes involved in muscle metabolism correlate well with the increase in net protein balance across the leg.