Sixteen consecutive patients who had ventricular preexcitation complicated by atrial fibrillation or flutter were treated with intravenous flecainide acetate after treatment with as many as 5 unsuccessful trial regimens with other drugs. In 15 patients who had atrial fibrillation, the shortest RR interval during spontaneous episodes was 210 +/- 39 ms (mean +/- standard deviation), and the average ventricular rate was 208 +/- 37 beats/min. Intravenous flecainide prevented induction of atrial fibrillation in 4 of 9 patients and eliminated anterograde accessory pathway conduction in 9 of the 16 patients. In 5 patients whose atrial fibrillation remained inducible and who continued to have preexcitation, the shortest preexcited RR interval increased from 185 +/- 29 to 281 +/- 46 ms (p less than 0.01). Fourteen patients who had favorable responses to intravenous flecainide were given an oral regimen of the drug. Oral treatment was discontinued early because of proarrhythmic effects in 2 patients, and after 2 1/2 months because of headaches in 1 patient. Eleven patients, 5 receiving concomitant beta-blockade therapy, have continued to receive a regimen of flecainide for a mean of 21 months (range 3 to 48). Seven patients have had no clinical recurrence of arrhythmias. Recurrences in 4 patients have been rare and brief with no changes in therapy required.