Sotalol has Class II and III antiarrhythmic effects. Its efficacy and safety as a treatment of atrial fibrillation in patients with the Wolff-Parkinson-White (WPW) syndrome is controversial. We evaluated the effects of isoproterenol and IV sotalol (1.5 mg/kg in 10 minutes) given together versus isoproterenol alone on anterograde conduction through the AV node and accessory pathway. Atrial fibrillation was induced in 22 patients with WPW (13 men, 9 women, 36 +/- 16 years old). AV node and accessory pathway conduction were both enhanced by isoproterenol, although the effect was greater on the AV node. The minimum interval between preexcited QRS complexes shortened in all patients. Conversely, sotalol caused a significant prolongation of the shortest preexcited QRS interval as well as of the shortest interval between narrow QRS complexes. In addition, sotalol reversed all the effects of isoproterenol during atrial fibrillation. The percent of preexcited QRS complexes was not significantly modified because variations in ventricular preexcitation results from a balance between the relative effects on refractoriness of the accessory pathway versus of the AV node and in the amount of respective anterograde and retrograde concealed conduction. There were no serious adverse effects. Reversion to sinus rhythm was documented in 12 patients (60%). These short-term observations suggest that sotalol may be safe and effective in the treatment of patients with WPW and atrial fibrillation.