Ventricular tachyarrhythmias are the major clinical manifestation of arrhythmogenic right ventricular disease. Although antiarrhythmic therapy has been widely advocated, there is only limited information available on the efficacy of antiarrhythmic drugs in these patients. The short- and long-term efficacies of various antiarrhythmic agents were retrospectively and prospectively analyzed in 81 patients (mean age, 39 +/- 14 years; range, 16-68 years; 61.7% males) with arrhythmogenic right ventricular disease. In 42 patients with inducible ventricular tachycardia during programmed ventricular stimulation, the following efficacy rates were obtained: class Ia and Ib drugs (n = 18), 5.6%; class Ic drugs (n = 25), 12%; beta-blockers (n = 8), 0%; sotalol (n = 38), 68.4%; amiodarone (n = 13), 15.4%; verapamil (n = 5), 0%; and drug combinations (n = 26), 15.4%. Only one of the 10 patients not responding to sotalol was treated effectively by amiodarone, whereas the remaining nine patients proved to be drug refractory toward all other drugs tested (3.8 +/- 2.3 drugs, including amiodarone in five cases) and underwent nonpharmacological therapy. During a follow-up of 34 +/- 25 months, three of the 31 patients (9.7%) discharged on pharmacological therapy had nonfatal recurrences of ventricular tachycardia after 0.5, 51, and 63 months, respectively. In 39 patients with noninducible ventricular tachycardia during programmed ventricular stimulation, the following efficacy rates were observed: class Ia and Ib drugs (n = 16), 0%; class Ic agents (n = 23), 17.4%; beta-blockers (n = 7), 28.6%; sotalol (n = 35), 82.8%; amiodarone (n = 4), 25%; verapamil (n = 24), 50%; and drug combinations (n = 11), 9.1%. During a follow-up of 14 +/- 13 months, four of 33 patients (12.1%) discharged on antiarrhythmic drugs had nonfatal relapses of their clinical ventricular arrhythmia. Thus, in arrhythmogenic right ventricular disease, sotalol proved to be highly effective in patients with inducible as well as noninducible ventricular tachycardia. Patients with inducible ventricular tachycardia not responding to sotalol are likely to not respond to other antiarrhythmic drugs and should be considered for nonpharmacological therapy without further drug testing. Amiodarone did not prove to be more effective than sotalol and may not be an alternative because of frequent side effects during long-term therapy, especially in young patients. Verapamil and beta-blockers were effective in a considerable number of patients with noninducible ventricular tachycardia and may be a therapeutic alternative in this subgroup. Class I agents appear to be rarely effective in the treatment of both inducible and noninducible ventricular tachycardia in arrhythmogenic right ventricular disease.