The use of antiarrhythmic drugs to suppress ventricular arrhythmias in pediatric patients with a structurally or hemodynamically abnormal heart appears to improve long-term prognosis. The previously successful use of phenytoin to treat serious ventricular arrhythmias led to the investigation for an alternative antiarrhythmic agent, in the same antiarrhythmic drug class, for those patients who develop side effects or become intolerant to phenytoin's antiarrhythmic effect. Forty-two children and young adults (age range 5 months to 34 years, mean 15.5 years) were treated with mexiletine. Arrhythmias treated were ventricular tachycardia (25), ventricular couplets (8), multiform ventricular premature beats (4) and frequent uniform ventricular premature beats (5). Anatomic diagnoses included congenital heart disease (postoperative in 26, unoperated in 2), cardiomyopathy (7), no heart disease (4) and other (3). Thirty-three patients had been previously treated with 1 to 5 (mean 1.6) antiarrhythmic drugs. In the short term, ventricular arrhythmias were effectively suppressed in 30 (71%) of all 42 patients treated. During follow-up (ranging to 42 months, median 10.6), 18 (60%) of the 30 acute responders continued to have excellent control. Early suppression of ventricular arrhythmias was more effective in patients with congenital heart disease (89%) than in those with cardiomyopathy (29%) or no heart disease (43%) (p less than 0.01). Initial complexity of ventricular ectopic activity had no effect on treatment results. Of 25 patients previously treated with phenytoin, in whom alternative antiarrhythmic therapy was required, 40% had long-term arrhythmia control when treated with mexiletine. Mexiletine therapy was terminated for side effects in only five patients (12%). Mexiletine is recommended for young patients with congenital heart disease and serious ventricular arrhythmias.