We studied the pattern of endocardial and epicardial activation during normal sinus rhythm and ventricular arrhythmias in 42 mongrel, dogs immediately after coronary artery ligation. The electrocardiogram (ECG) and seven single or composite electrograms were recorded from various endocardial and epicardial sites within and surrounding the ischemic area. Fragmentation and diastolic conduction delay originating in the central ischemic epicardial area preceded the appearance of ventricular arrhythmias during sinus rhythm and normal AV conduction. In all experiments, the activation pattern in the ischemic zone following diastolic epicardial bridging was associated with early spread into the ischemic endocardial zone, and then to all the remaining protions of the heart. We never observed direct epicardial spread to the normal areas of the heart. Likewise, evidence of automatic activity could not be detected during this period of acute ischemia. Isolated premature endocardial activation was frequently noted late in diastole. Progressive earlier endocardial activation in the ischemic zone was associated with the emergence of manifest ventricular arrhythmias. Delayed epicardial activation and fragmentation appeared to engender rapid and irregular endocardial activation, which then appeared to be transmitted to the normal epicardium and to produce ventricular arrhythmias and fibrillation. The ischemic endocardial area may play an important role in the genesis of the dangerous reentrant ventricular arrhythmias associated with acute ischemia.