Use of mexiletine was evaluated in 313 patients with ventricular tachyarrhythmias refractory to conventional antiarrhythmic drugs. Therapy with mexiletine was continued long term in 107 patients who responded to the drug and were free of side effects during a short-term evaluation in hospital. During an average follow-up of 22.8 months (0.1 to 70 months), 19 patients died (17.8%). Eleven patients had sudden death (3.6% per year), while six patients died of progressive congestive heart failure and two of noncardiac causes. Nonfatal ventricular arrhythmia recurred in 14 patients (4.9% per year). Overall, 25 patients had recurrent arrhythmia (incidence of 5.5% per year). Side effects occurred in 13 patients after an average of 5.1 months and were primarily gastrointestinal and neurologic. Sixty-one patients (57%) have continued on mexiletine therapy for an average of 32.2 months (1 to 70 months). Outcome during long-term therapy was not related to drug dose, blood level, or presenting arrhythmia. We conclude that if therapy with mexiletine is carefully evaluated and individualized, the drug is effective and well tolerated during long-term use.