In order to assess the efficacy and safety of oral indecainide in patients with serious ventricular arrhythmias we studied 11 patients with high-grade ventricular ectopy and ventricular tachycardia (VT) which were refractory to therapy with at least one standard antiarrhythmic drug. Spontaneous arrhythmias were quantitated by 24-h Holter monitor before and during therapy with indecainide. Spontaneous VT was sustained in 4 patients and nonsustained in 7. Ten patients underwent baseline electrophysiologic study (EPS) and VT was induced in 9. The mean ejection fraction was 25 +/- 14%. Indecainide was given orally at a dose of 211 +/- 118 mg/day. The frequency of ventricular premature beats (VPBs) was significantly (greater than 85%) decreased in 90% of patients, while ventricular couplets frequency decreased in 78%. Spontaneous VT was abolished in 5 of 11 (45%). Sustained VT was induced in 5 of 7 (71%) patients who underwent follow-up EPS. The QRS duration was significantly prolonged during therapy (0.13 +/- 0.04 s) compared to control (0.10 +/- 0.02 s). The PR, QTc, and JTc intervals were not significantly changed. Indecainide was well tolerated, but 2 patients died of ventricular tachyarrhythmias while receiving the drug. Indecainide suppressed VPBs in a high percentage of patients, but was much less successful in controlling VT. Caution is necessary when using this drug because of its potential for exacerbation of arrhythmia.