Thirty mongrel dogs underwent proximal occlusion of the left anterior descending coronary artery to evaluate the comparative action of mexiletine and lidocaine on ventricular arrhythmias during myocardial reperfusion. Heart rate, arterial blood pressure, left ventricular end-diastolic pressure and dp/dt max were evaluated before and at the 20th and 25th min after coronary occlusion; at the 25th min coronary occlusion was removed. Dogs were randomly assigned to one of the following groups of 10: 1) control group; 2) dogs given i.v. mexiletine; 3) dogs given i.v. lidocaine. As expected, during ischemia, myocardial contractility decreased after mexiletine or lidocaine administration more than in the control group. Ventricular arrhythmias during myocardial reperfusion occurred in 9 dogs of the control group (ventricular tachycardia in 2 cases and ventricular fibrillation in 7 cases). Among dogs given mexiletine only 1 had ventricular fibrillation (p less than 0.001 vs control). Six of the 10 dogs given lidocaine had ventricular arrhythmias (ventricular tachycardia in 5 cases and ventricular fibrillation in 1 case) (p = ns vs control group; p less than 0.05 vs mexiletine group). Thus mexiletine and lidocaine had similar effects on cardiac function during myocardial ischemia and only mexiletine showed a protective effect against reperfusion ventricular arrhythmias.