Using an isolated perfused rat heart preparation, the protective effects of lidocaine and diltiazem on ischemic derangements of myocardial energy metabolism were studied with ³¹P-nuclear magnetic resonance spectroscopy. The hearts were perfused with a solution containing lidocaine (4.27×10^-5, 12.80×10^-5M) or diltiazem (2.22×10^-7, 2.22×10^-6M) for 15min prior to the induction of global ischemia. The decrease in myocardial oxygen consumption rate, assessed as the product of heart rate and left ventricular systolic pressure (HR×LVP), was greater in diltiazem-treated than in lidocaine-treated hearts. Diltiazem and lidocaine significantly retarded the fall in myocardial pH during ischemia and improved ATP recovery after reperfusion. There was a good correlation between suppression of HR×LVP observed before induction of ischemia and decreased drop in pH during the early phase of ischemia in the diltiazem-treated groups (r=-0.78, p<0.01), but not in the lidocaine-treated groups. These results indicate that the beneficial effects of diltiazem on the ischemic myocardium are due primarily to the cardiodepressant effects. The beneficial effects of lidocaine cannot, however, be explained solely on the basis of the depression of oxygen consumption.