The actions of the beta-adrenergic receptor antagonist, d,l-nadolol, were examined in anesthetized dogs subjected to circumflex coronary artery ligation in the presence of previous anterior myocardial infarction. With circumflex ligation, control dogs (N = 18) developed premature ventricular beats and ventricular tachycardia, followed by ventricular fibrillation (N = 16, 89%). Immediate arrhythmias (2 to 5 minutes) were accompanied by activation delays and continuous diastolic electrical activity in acutely ischemic epicardial tissue. Delayed arrhythmias (6 to 12 minutes) were accompanied by delayed activation and continuous diastolic electrical activity in acutely ischemic mid-myocardium. Nadolol (8 mg/kg, intravenously) (N = 10) reduced ventricular arrhythmias during both phases of arrhythmia development and increased survival (70%, p = 0.001 vs control). Nadolol failed to after activation in acutely ischemic epicardium, but prevented beat-to-beat changes in epicardial and mid-myocardial activation. Atrial pacing of nadolol-treated animals at heart rates comparable with those of the control group reversed the beneficial effects of nadolol on the development of ventricular arrhythmias and ventricular fibrillation (70%; p = 0.07 vs nadolol; p = 0.21 vs control, respectively). The beneficial effects of nadolol could not be attributed to reduced epicardial delays, but were associated with the suppression of beat-to-beat conduction abnormalities that preceded ventricular fibrillation.