Protein turnover in cardiac and skeletal muscle is affected by the provision of amino acids, particularly the branched chain amino acids (BCAA). The effect of each of the BCAA, valine, leucine, and isoleucine, on the systolic function of isolated normal or septic rat heart perfused as a Langendorff preparation was examined. Thirty normal control and 28 septic rats (cecal ligation and puncture) were perfused with either Krebs + 8.5 mM glucose or Krebs + 5.0 mM glucose and 3.5 mM valine, leucine, or isoleucine. Septic hearts perfused with Krebs + 8.5 mM glucose exhibited developed force (DF) and force velocity (dF/dt) levels which were reduced to an average of 45 and 50%, respectively, compared to normal controls, and improved by 35% during 60 min perfusion over measurements made at time zero. In normal hearts DF and dF/dt decreased significantly during perfusion with leucine (27%) and isoleucine (20%). In sepsis, perfusion with leucine and isoleucine resulted in a mild improvement in systolic function. However, valine was far less effective than leucine and isoleucine in maintaining systolic function in sepsis, due apparently to valine being a less efficient energy substrate for the cardiac muscle in a state of severe energy deficit. Thus, valine, leucine, and isoleucine seem to exert different effects on the systolic function of normal and septic isolated rat hearts.