Programmed ventricular stimulation was used to test oral bethanidine sulfate in 10 patients with life-threatening ventricular arrhythmias. These patients had previously documented, recurrent, sustained ventricular tachycardia (VT) and/or ventricular fibrillation (VF) complicating stable heart disease. During control electrophysiologic studies, VT could be induced in all 10 patients: 6 with nonsustained VT, 3 with sustained VT, and 1 with VT/VF. After control, bethanidine 20-30 mg/kg was administered orally and beginning 60 minutes later, programmed ventricular stimulation was repeated. After bethanidine administration, VT could be induced in nine patients; in four, the VT was essentially unchanged from that induced during control studies. In four others, worse VT was induced after bethanidine. The remaining two patients had a potentially beneficial response to the drug. Bethanidine was poorly tolerated: seven patients had symptomatic orthostatic hypotension that persisted for several days despite concurrent protriptyline therapy. Furthermore, in four patients, spontaneous VT or VT/VF occurred 3-8 hours after the last dose. Nausea, vomiting, flushing, and blood pressure elevation were also noted. Bethanidine sulfate in the dosages used usually does not prevent the induction of VT by programmed ventricular stimulation and frequently causes serious toxicity. These findings suggest that the drug would be ineffective and poorly tolerated for long-term therapy in patients with serious ventricular arrhythmias.