In a double-blind study involving 165 patients we examined the role of mexiletine, a new antiarrhythmic drug, for the prophylaxis of ventricular arrhythmias after acute myocardial infarction. Mexiletine or placebo was given orally to patients on arrival in the coronary care unit, and continuous electrocardiographic tape recordings were used to document arrhythmias. Ventricular tachycardia and R-on-T ventricular ectopic beats were significantly reduced in the mexiletine patients, but too few episodes of ventricular fibrillation occurred for statistical comment. When arrhythmias did occur in the mexiletine group, it was usually early in the study, at which time plasma drug levels were low. Adverse effects were uncommon. Patients who were given therapy, but in whom acute myocardial infarction could not be confirmed, suffered no serious consequences of taking mexiletine. The results demonstrate the benefit and limitations of prophylactic oral antiarrhythmic therapy for patients with acute myocardial infarction.