The present study determined whether burn injury decreases myocardial protein synthesis and potential contributing mechanisms for this impairment. A 40% total body surface area full-thickness scald burn was produced in anesthetized rats and animals studied 24 h later. Burn decreased the in vivo-determined rate of myocardial protein synthesis and translation efficiency. Several eukaryotic initiation factors (eIFs) and elongation factors (eEFs) were examined to identify potential mechanisms for regulating mRNA translation. Burn failed to alter eIF2B activity or the total amount or phosphorylation status of either eIF2 or eIF2B. In contrast, hearts from burned rats demonstrated a) increased binding of the translational repressor 4E-BP1 with eIF4E, b) decreased amount of eIF4E associated with eIF4G, and c) decreased phosphorylation of 4E-BP1. Furthermore, the phosphorylation of mTOR, S6K1, the ribosomal protein S6, and eIF4G were also decreased in hearts from burned rats. Burn did not appear to adversely affect elongation because there was no significant difference in the myocardial content of eEF1 or eEF2, or the phosphorylation state of eEF2. The abovementioned burn-induced change in eIF4E availability was associated with increases in the cardiac mRNA content for IL-1, IL-6 and HMGB1 (but not TNF) as well as impairment of in vitro myocardial performance. These data indicate that thermal injury specifically decreases cardiac protein synthesis in part by decreasing mRNA translation efficiency resulting from an impairment in translation initiation associated with alterations in eIF4E availability and S6K1 activity.