To determine whether combined intravenous (i.v.) and oral loading with amiodarone can shorten its onset of action, a comparative study was conducted. Twenty patients with refractory ventricular arrhythmias were treated with amiodarone. All patients had frequent (greater than or equal to 30/hour) and complex (repetitive) ventricular premature beats on a 48-hour baseline Holter recording. Ten patients (group A) received oral loading alone: 800 mg/day for 7 days, 600 mg/day for 3 days, then a maintenance dose 200 to 400 mg/day. Ten patients (group B) received i.v. and oral loading: 5 mg/kg i.v., and then the same regimen as for group A. Follow-up 24-hour Holter recordings were obtained daily for 7 days, weekly for 1 month, and then monthly. Arrhythmia control was defined as at least a 70% reduction in ventricular premature beats, a 90% or greater reduction in couplets and abolition of ventricular tachycardia. The time to optimal ventricular arrhythmia control was shorter for group B (20 +/- 18 vs 105 +/- 83 days, p less than 0.05) and the cumulative amiodarone dose at the time of control was smaller for group B (10 +/- 8 vs 48 +/- 39 g, p less than 0.05). No complications were encountered with i.v. amiodarone. Thus, initial loading with i.v. amiodarone can shorten the time to optimal ventricular arrhythmia control and lower the cumulative dose required.