The long-term efficacy and safety of flecainide (100 to 200 mg twice a day) were evaluated in 21 patients with high-grade, chronic ventricular arrhythmias who responded to and tolerated flecainide at a preliminary evaluation (200 mg, single oral dose). Antiarrhythmic response was evaluated at 3 days and 3, 6, 12, 18, and 24 months. The mean follow-up was 25 +/- 14 months (range 3 to 52). Four patients (19%) were excluded from efficacy analysis because of spontaneous decrease in baseline arrhythmia observed after 12 months of therapy. Effective arrhythmia suppression at both Holter monitoring and during exercise stress testing was maintained in 14 of 17 patients (82%). Mean frequency of premature ventricular contractions remained reduced by more than 95% throughout the follow-up. Five patients discontinued therapy between 3 and 18 months because of drug ineffectiveness (three patients, 18%) or side effects (two patients, 12%). In 12 patients (71%) long-term efficacy and tolerance were demonstrated. In no case was aggravation of arrhythmia or adverse cardiac effects observed. Side effects (5% to 29% of patients during follow-up) were usually minor and easily abolished by dosage reduction. In patients with chronic ventricular arrhythmias, flecainide maintained a favorable ratio between efficacy and side effects during a 2-year follow-up.