The ability of chronic bretylium tosylate treatment to prevent the induction of ventricular tachycardia was assessed in the conscious dog subjected to serial programmed ventricular stimulation on days 3-6 after acute myocardial infarction. In 34 untreated control dogs, programmed ventricular stimulation produced nonsustained ventricular tachycardia in 11 dogs (32%), sustained ventricular tachycardia in 10 (29%), and ventricular fibrillation in 10 (29%) on the third and fourth day after occlusion and reperfusion of the left anterior descending coronary artery. Bretylium tosylate, 5 mg/kg i.v., was given every 12 hours to a separate group of seven dogs after the induction of ischemic myocardial injury. Programmed ventricular stimulation on the third and fourth days after the induction of myocardial ischemic injury failed to elicit ventricular arrhythmias. Induction of arrhythmias by programmed electrical stimulation could be induced in each of the seven dogs; however, 36 hours after discontinuing bretylium tosylate, two dogs (29%) had non-sustained ventricular tachycardia and five (71%) had sustained ventricular tachycardia. When retested at 60 hours after withdrawal of bretylium tosylate, five (71%) had sustained ventricular tachycardia and two (28%) developed ventricular fibrillation. Readministration of bretylium tosylate (5 mg/kg, i.v.) to four of the five surviving dogs prevented the induction of ventricular arrhythmias in response to programmed ventricular stimulation. The results of these investigations suggest that bretylium tosylate may be effective in preventing the onset of reentrant ventricular rhythms after myocardial ischemic damage, and therefore may be of value in preventing sudden coronary death.