The early hemodynamic, metabolic and electrophysiological consequences of acute coronary artery ligation was studied in an experimental model which allows the simultaneous assessment of blood flow and sampling of blood from both normal and acutely ischemic zones of myocardium. The major metabolic changes which occur in the ischemic zone during the first 30 min after coronary artery ligation are increases in PCO2 [partial pressure of CO2], decreases in pH and O2 content, a shift in lactate handling from extraction to production and an efflux of K+. These changes were not observed in coronary sinus blood draining essentially non-ischemic zones of myocardium. The major hemodynamic change produced by coronary artery ligation was cardiac depression (decreased stroke volume and cardiac work), unchanged LV dP/dt [left ventricular change in pressure over time] with an elevated filling pressure. Acute ligation of the anterior descending branch of the left coronary artery [l.a.d.] resulted in bursts of ventricular ectopic activity which was especially marked 10-20 min after ligation and which frequently resulted in ventricular fibrillation. The incidence of arrhythmias could be modified by the species of dog used, the anesthetic employed, the arterial O2 tension and the administration of several antiarrhythmic drugs. The possible relevance of the metabolic changes and the decreases in temperature observed in the ischemic myocardium, to the genesis of these arrhythmias is discussed. The changes in the ST-segment of epicardial leads produced by short (3 min) occlusions of the l.a.d. were studied in mongrel dogs. The evolution of ST-segment elevation may be linked to the efflux of K+ from ischemic myocardial cells.