Effects of L-carnitine on ventricular arrhythmias and myocardial metabolism in a reperfused ischemic myocardium were studied in 35 anesthetized mongrel dogs. The left anterior descending coronary artery was ligated for 40 min and then reperfused for 15 min. L-carnitine (100 mg/kg) was administered intravenously 5 min before the coronary ligation and infused continuously at a rate of 20 mg/kg/min from 5 min before the reperfusion to the end of the experiment. Electrocardiograms were recorded continuously throughout the experiment. Transmural myocardial samples were obtained from both the ischemic and the nonischemic areas after 15 min of reperfusion and used for the determination of ATP, free carnitine, long chain acyl carnitine and long chain acyl CoA. L-carnitine significantly reduced the incidence rate of ventricular fibrillation after reperfusion (from 29% in the controls to 5%, p < 0.05). ATP in the ischemic myocardium in the L-carnitine group was significantly higher than that in the control group (p < 0.05). Free carnitine in the control group significantly decreased in the ischemic area as compared with the nonischemic area (p < 0.01). In L-carnitine group, on the other hand, no difference was observed between them. Long chain acyl CoA in the control group significantly increased in the ischemic area as compared with the nonischemic area (p < 0.01). In L-carnitine group, on the other hand, no difference was observed between them. Thus, the accumulation of long chain acyl CoA in the ischemic myocardium was reduced by the L-carnitine treatment. These data suggest that L-carnitine has protective effects on ventricular arrhythmias and on metabolic changes after coronary artery reperfusion following coronary artery occlusion.