To evaluate the efficacy and safety of oral amiodarone in the treatment of recurrent, sustained, refractory ventricular arrhythmias, rapid high-dose oral loading was used to treat 12 critically ill patients with frequent, sometimes incessant, sustained ventricular arrhythmias refractory to 2 to 6 antiarrhythmic agents. Presenting arrhythmias included sustained monomorphic ventricular tachycardia and ventricular fibrillation associated with cardiac arrests in 6 patients. Patients experienced 2 to 10 episodes (mean 5 ± 2) of sustained ventricular arrhythmias over a mean period of 6.2 ± 5.0 days (range 1 to 14) before oral amiodarone was initiated at 1,200 to 1,400 mg/day. This included at least 1 to 4 episodes (mean 2.2 ± 1.1) within 24 hours before amiodarone. One to 4 antiarrhythmic drugs were administered concurrently during amiodarone loading. Sustained ventricular arrhythmias no longer occurred after a mean of 5.2 days (range 1 to 22) with amiodarone. Arrhythmias were controlled in 4 patients within 24 hours, 5 patients within 48 hours, 7 patients within 4 days and 10 patients within 6 days. Patients experienced a mean of 0.6 ± 0.8 episodes within 24 hours after amiodarone. Nine patients survived to hospital discharge. No patient had significant adverse effects during high-dose loading. In conclusion, high-dose oral amiodarone loading, when added to previously unsuccessful conventional antiarrhythmic therapy, is safe and often rapidly effective for at least short-term control of frequent, refractory, sustained ventricular arrhythmias.