We studied 25 anesthetized and thoracotamized dogs before and during 5 hours of acute regional myocardial ischemia. Krypton-81m (81mKr) was infused constantly into the aortic sinuses. The myocardial equilibrium of this tracer was used to image and assess the distribution of regional myocardial perfusion using a gamma camera and digital computer. The epicardial ECG was recorded, S-T segment elevation and the loss of R and appearance of Q waves were measured, and the plasma activity of creatine kinase (CK) was determined in aortic and coronary venous blood throughout these experiments. Ten dogs underwent left anterior descending coronary artery (LAD) narrowing for 5 hours and received no drugs. Five dogs received nifedipine 13 microgram/kg, and another five received 1.0 microgram/kg intravenously 30 minutes after LAD narrowing. Those dogs receiving nifedipine, 13 microgram/kg, showed a 30% fall in aortic pressure, a 12% rise in heart rate, and an extension of regional ischemia. The ECG showed an extension of infarct size, and CK release into the coronary vein appeared earlier than in the controls. Dogs receiving nifedipine, 1 microgram/kg, showed a 12% fall in blood pressure, no rise in heart rate, an improvement in regional perfusion, and ECG signs that suggested limitation of infarct size. There also was delayed release of coronary venous CK. The effects of nifedipine on the natural history of regional myocardial perfusion, the electrocardiogram, and enzyme release from the heart were dose related and cannot be generalized. These observations warrant further clinical investigation to improve the use of this agent in man.