The effect of a 14-day administration of FK-506 at 1 or 3 mg/kg on plasma lipids and myocardial energy and glucose metabolism in rats was investigated. FK-506 increased the level of blood glucose in rats when given daily at an oral dosage of 3 mg/kg for 14 days. The plasma level of total cholesterol was significantly increased by FK-506 at either 1 or 3 mg/kg, whereas that of triglyceride was not changed. There was no significant difference in energy charge potential and the lactate/pyruvate ratio of the myocardial tissue between FK-506- and solvent-treated groups. Because FK-506 administration for 14 consecutive days did not disturb myocardial energy and glucose metabolism, its cardiotoxic side effects were not recognized in the present experimental toxicological evaluation of rats.