We compared the ability of a new amiodarone-like agent, SR 33589, with that of amiodarone, D,L-sotalol, and lignocaine to reduce the incidence of ventricular fibrillation (VF) and associated arrhythmias caused by acute coronary artery occlusion in anesthetized pigs. Ischemia was induced by occlusion of the left coronary descending artery (LAD) for 30 min. Premature ventricular complexes (PVCs), ventricular tachycardia (VT), and ventricular fibrillation (VF) were recorded during coronary occlusion. SR 33589 (1.25, 2.50, and 5 mg/kg intravenously, i.v.) markedly reduced the occurrence of ventricular arrhythmias during ischemia. The incidence of VF was reduced from 90% in the control group to 30% (p < 0.05) with 1.25 mg/kg, to 10% (p < 0.001) with 2.50 mg/kg, and to 20% (p < 0.01) with 5 mg/kg. In addition, SR 33589, especially at the two higher doses, caused a sustained reduction in both the incidence of VT and the number of PVCs per minute. In comparison, amiodarone 10 and 20 mg/kg i.v. reduced the incidence of VF (40 and 50%, respectively), but these reductions never reached a level of statistical significance. The incidence of VT and the number of PVCs per minute were also decreased significantly by amiodarone. D,L-sotalol 3 mg/kg i.v. exerted significant anti-arrhythmic activity; the incidence of VF was reduced 20% (p < 0.01), and both the incidence of VT and number of PVC per minute were also reduced. In contrast, lignocaine given as a 2-mg/kg bolus followed by an infusion at 70 micrograms/kg/min had no antiarrhythmic or antifibrillatory activity in this preparation.(ABSTRACT TRUNCATED AT 250 WORDS)