Prophylactic administration of antiarrhythmic agents may decrease mortality from sudden arrhythmias among ambulatory patients with coronary heart disease. Long-term prophylactic therapy presupposes identification of subgroups at greatest risk of sudden death, such as survivors of myocardial infarction with persistent ventricular ectopic activity. Better antiarrhythmics are urgently needed, since procainamide and quinidine, presently the most effective drugs, are poorly tolerated by many patients during long-term use. Antiarrhythmic drugs can also be administered prophylactically by trained personnel or by the patient upon first suspicion of acute myocardial infarction regardless of arrhythmic activity. Intramuscular administration of lidocaine hydrochloride (300 mg) or procainamide hydrochloride (750 mg) rapidly produces antiarrhythmically effective blood levels which persist for 1.5 and 2.5 hours, respectively, and are unlikely to cause adverse cardiovascular effects. Large-scale, controlled, prospective studies are required to evaluate the effectiveness of these approaches.