Antiarrhythmic and electrophysiologic actions of bethanidine sulfate, a chemical analog of bretylium tosylate, were studied using programmed cardiac electrical stimulation in 14 survivors of out-of-hospital cardiac arrest unassociated with acute myocardial infarction. Before bethanidine sulfate was administered sustained ventricular tachyarrhythmias (VT) were inducible in 11 patients and reproducible nonsustained VT was induced in 3 patients. Bethanidine sulfate shortened sinus cycle length and absolute and relative ventricular refractory periods measured during sinus rhythm, but did not alter ventricular effective refractory period measured during ventricular pacing. Bethanidine sulfate prevented inducible VT in 8 patients (57%), increased the number of extrastimuli needed to induce VT in 2 patients, and was ineffective in 4 patients. In contrast, in only 1 of 26 trials with other conventional and investigational antiarrhythmic drugs in these patients was VT prevented. Orthostatic hypotension was a prominent side effect of bethanidine sulfate therapy, but could be reversed in most patients by concomitant administration of protriptyline. Five patients in whom bethanidine sulfate was effective in the laboratory have been treated chronically (400 to 600 mg 4 times daily), and all are alive at 3 to 40 months. In the remaining 9 patients, 8 were treated empirically because no drug was effective in the laboratory and 1 was treated with quinidine, which appeared to be protective during testing. Four of these 9 patients, including the patient treated with quinidine, died suddenly during follow-up. Thus, although bethanidine sulfate therapy is difficult to initiate because of orthostatic hypotensive side effects, it may be useful in treating patients at high risk of recurrent cardiac arrest.