In a randomized, double-blind, controlled study of 98 patients with atrial fibrillation (AF) (present for > or = 30 minutes, < or = 72 hours, and a ventricular response of > or = 100 beats/min), intravenous flecainide (2 mg/kg, maximum 150 mg) was compared with intravenous amiodarone (7 mg/kg) and placebo. Exclusion criteria included significant left ventricular dysfunction, inotrope dependence, recent antiarrhythmic therapy, hypokalemia, and pacemaker dependence. Reversion to stable sinus rhythm within 2 hours of starting medication was considered likely to be due to drug effect. Twenty of 34 patients (59%) given flecainide, 11 of 32 (34%) given amiodarone, and 7 of 32 (22%) given placebo reverted to stable sinus rhythm in < or = 2 hours after starting medication (chi-square 9.87, p = 0.007). More patients reverted to stable rhythm with flecainide than with placebo (p = 0.005; odds ratio 5.1, 95% confidence interval 1.54 to 17.5). There was no significant difference between amiodarone and placebo or between flecainide and amiodarone. However, after 8 hours there were no significant differences in reversion between the treatment groups: flecainide (n = 23, 68%), amiodarone (n = 19, 59%), and placebo (n = 18, 56%). Amiodarone promptly reduced the ventricular rate, and this effect was maintained for 8 hours in those whose reversion to stable sinus rhythm was unsuccessful: flecainide was no more effective than placebo in controlling ventricular rate. Adverse effects were not significantly different in the 3 groups. Thus, intravenous flecainide results in earlier reversion of AF than does intravenous amiodarone or placebo. Amiodarone, although less effective in reverting AF, slows the rapid ventricular response.(ABSTRACT TRUNCATED AT 250 WORDS)