Amiodarone is effective for long-term maintenance of sinus rhythm after electrical cardioversion of refractory atrial fibrillation or flutter. To examine its efficacy and safety for pharmacologic conversion of these arrhythmias, we studied 129 patients with refractory atrial fibrillation or flutter who had failed previous intensive conventional antiarrhythmic treatment. In anticipation of electrical cardioversion, patients were loaded with amiodarone, 600 mg/day during a 4-week period. The main outcome measure was pharmacologic conversion during this period. During the loading period, 23 patients (18%) converted to sinus rhythm. When analyzed in a multivariate model, conversion was related to desethylamiodarone plasma level (p = 0.0006), arrhythmia duration (p = 0.04), left atrial area (p = 0.02), and concomitant treatment with verapamil (p = 0.01). During ongoing atrial fibrillation after loading, the ventricular rate decreased from 100 +/- 25 to 87 +/- 27 beats/ min (p <0.001). Amiodarone appeared to be safe and did not have to be discontinued because of intolerable side effects. Thus, amiodarone loading is safe and is still able to convert refractory atrial fibrillation or flutter. Conversion is related to increased desethylamiodarone plasma levels and concomitant treatment with verapamil. Because prolonged loading may increase desethylamiodarone plasma concentrations, this may enhance efficacy and obviate the need for electrical cardioversion.