The effect of oxygen therapy or the administration of procainamide, reserpine, or propranolol hydrochloride on reflow ventricular fibrillation (VF) and myocardial necrosis was assessed in dogs whose left circumflex coronary artery was occluded for 20 minutes. Neither oxygen nor procainamide therapy altered the incidence of VF or necrosis significantly when compared to controls. Reserpine decreased VF developing upon the return of coronary blood flow but had no effect on necrosis. Propranolol did not alter the incidence of VF but significantly reduced the incidence of necrosis after transient episodes of ischemia of either 20 or 25 minutes' duration. The prevention of myocardial cell necrosis by propranolol therapy is the first direct demonstration that it is possible to delay the onset of necrosis in vivo in acute ischemic injury.