Ten patients were treated with oral indecainide for frequent ventricular ectopic depolarizations during a short-term, dose-ranging, single blind inpatient trial followed by open label long-term therapy for 2 years. During dose ranging, patients received placebo followed by 50, 75 and 103 mg of indecainide three times daily. Eight of the 10 patients achieved ≥80% reduction in ventricular ectopic depolarizations during inpatient therapy. Mean ventricular ectopic depolarizations decreased from 15,792/24 h to 2,357/24 h on optimal dosage (p < 0.01). Nine patients had paired ventricular ectopic depolarizations; four of the nine had ≥99% reduction of these beats. Among seven patients with nonsustained ventricular tachycardia, five had 100% elimination of these events with indecainide and all had ≥90% reduction in these events. Indecainide prolonged the PR interval 44 ± 27 ms (p < 0.0001) and the QRS interval 11 ± 9 ms (p < 0,0901) from baseline without prolongation of the QTc or JTc interval. The mean trough plasma level of indecainide on optimal dosage was 409 ± 173 ng/ml and the mean plasma elimination half-life was 10.3 ± 2.3 h (range 7.1 to 14.2). No adverse hemodynamic effects of indecainide were detected. Side effects during short-term therapy were mild and did not require discontinuation of the drug. Efficacy was maintained for some patients during long-term therapy for 2 years, although five patients discontinued therapy because of loss of efficacy or side effects. Indecainide is a highly effective and well tolerated antiarrhythmic drug for suppression of frequent and repetitive ventricular ectopic depolarizations.