Combination antiarrhythmic drug therapy may be more effective than treatment with a single agent for control of refractory cases of sustained ventricular tachycardia (VT). In a prospective randomized crossover study of 20 patients with impaired left ventricular function (ejection fraction of 28% +/- 8%) and recurrent VT in spite of treatment with amiodarone, we compared the efficacy and safety of adjuvant therapy with metoprolol, 50 mg two times daily and xamoterol, 200 mg two times daily. Metoprolol caused hemodynamic deterioration in five patients, and only one also experienced intolerance to xamoterol. Sustained VT was inducible in all 20 patients who were receiving amiodarone alone but was suppressed or rendered nonsustained in 8 of 20 patients during treatment with amiodarone plus xamoterol and in 6 of 17 patients during treatment with amiodarone plus metoprolol. Addition of xamoterol restored sinus rhythm in four patients who presented with incessant VT, and metoprolol was effective for three of them. Neither beta-blocker significantly altered tachycardia cycle length or any electrophysiologic parameter other than the slowing of the sinus rate. Both beta-blockers suppressed exercise-induced VT in 3 of 4 patients, and addition of xamoterol significantly increased treadmill exercise duration (7.1 +/- 1.8 min) compared with administration of amiodarone alone (3.8 +/- 1.5 min; p < 0.01). Fourteen patients were discharged with prescriptions for amiodarone-beta-blocker combinations. During a mean follow-up period of 13 months (range, 2 to 24 months), there were three cases of recurrent VT (in all patients VT remained inducible) and no sudden deaths.(ABSTRACT TRUNCATED AT 250 WORDS)