Sotalol is a unique beta-blocker that lengthens cardiac repolarization and effective refractory period (ERP). Its efficacy after intravenous (1.5 mg/kg) and oral (160 to 480 mg bid) administration was therefore evaluated in 37 patients with refractory recurrent ventricular tachycardia/fibrillation (VT/VF). Thirty-five patients, 33 with inducible VT/VF, underwent electrophysiologic testing. Intravenous sotalol lengthened the ERP in the atrium (+24.6%, p less than .01), atrioventricular node (+24.9%, p less than .01), and ventricle (+14.9%, p less than .01). It also significantly lengthened sinus node recovery time, corrected QT interval (QTc), and the AH interval, but not the HV interval. Sotalol prevented reinduction of VT/VF in 15 patients (45.5%). Twenty-five of the 33 patients (15 with positive results of electrophysiologic tests; 10 with negative results) were given oral sotalol. The drug was ineffective in seven (26.9%) and aggravated arrhythmia in one (3.8%). In four patients sotalol was withdrawn because of side effects; arrhythmias recurred late in two (7.7%). Eleven patients (42.3%) have continued on oral sotalol over a mean follow-up period of 9.2 +/- 8.6 months. Sotalol reduced (n = 21) total premature ventricular complex (PVC) count on the Holter electrocardiogram by 73% (p less than .01), paired PVCs by 89% (p less than .01), and beats of ventricular tachycardia by 95% (p less than .01). In 52% (n = 11), total reduction in PVCs was at least 85%, and incidence of paired and tachycardiac beats was reduced at least 90% (group A). In the remainder (n = 10), PVC suppression was not significant (group B). Group A included nine patients with nonreinducible VT/VF and two in whom it was reinducible; in group B, eight of 10 patients had reinducible VT/VF. The difference between the two groups (Fisher exact test) was significant (p less than .01). The prevention of reinduction of VT/VF by intravenous sotalol and suppression of spontaneously occurring arrhythmias by the oral drug were both predictive of long-term drug efficacy. Sotalol is a significant advance in the short- and long-term management of life-threatening ventricular tachyarrhythmias.