The antiarrhythmic efficacy of mexiletine hydrochloride (Mexitil) was evaluated in 100 patients with potentially lethal and drug-resistant ventricular arrhythmia. The efficacy of arrhythmia suppression was assessed by Holter monitoring. The overall arrhythmia suppression of ventricular premature contractions of 70% and greater was low and seen in only 22% of patients, with an additional 16% responding to a combination of mexiletine and an additional antiarrhythmic drug. The suppression of high-grade forms, couplets of 90% and greater, and complete abolition of nonsustained runs of ventricular tachycardia was achieved in 22% of patients, with 9% responding to the addition of another antiarrhythmic agent. Ventricular premature contractions, couplets, and nonsustained ventricular tachycardia were suppressed in only 16% of the cohort. The drug was poorly tolerated, with intolerable side effects developing in 49% of patients receiving mexiletine alone and in 57% of patients receiving a combination of antiarrhythmic agents. Tolerable adverse effects were relatively common but transient and dose related.