A 24 h intravenous dosing regimen of amiodarone was designed to reach a peak plasma concentration at 1 h and to maintain the concentration above a certain level during the infusion period. A randomized, open-label, digoxin-controlled study was undertaken to observe the efficacy and safety of the dosing regimen of amiodarone in treating recent-onset, persistent atrial fibrillation and flutter with ventricular rates above 130 beats . min(-1). Fifty patients with a mean age of 70 +/- 7 (SD) years were enrolled and randomly assigned to receive either amiodarone intravenously (n=26) or digoxin (n=24). Amiodarone HCl was infused over 24 it according to the following regimen: 5 mg . min(-1) 3 mg . min(-1), 1 mg . min(-1) and 0.5 mg . min(-1) for 1, 3, 6 and 14 h, respectively, for a 70-kg subject. Digoxin (0.013 mg . kg(-1)) was infused in three divided doses, each dose 2 h apart and infused over 30 min. The mean heart rates in the amiodarone group decreased significantly from 157 +/- 20 beats . min(-1) to 122 +/- 25 beats . min(-1) after 1 h (P<0.05 vs baseline), and then decreased further to stabilize at 96 +/- 25 beats . min(-1) after 6 h (P<0.05). The digoxin group had fewer dramatic alterations in heart rates, compared to the amiodarone group, in the first 8 h (P<0.05, respectively). Maximum reduction was reached only after gh. The amiodarone infusion was prematurely aborted in two patients due to severe bradycardia and death after conversion in one patient and aggravation of heart failure in the other. Overall, 24 of 26 patients (92%) in the amiodarone group and 17 of 24 (71%) in the digoxin group were restored to sinus rhythm within 24 h. The accumulated rates of conversion over 24 h were significantly different between the two groups (P=0.0048). Digoxin, while not as effective as amiodarone in the treatment of recent-onset atrial fibrillation amd flutter, appears to be safer. Therefore, we suggest the use of digoxin as the first line drug for the type of patients that formed the basis of the current study and reserve amiodarone for refractory cases or those in whom digoxin is not suitable.