Although exercise testing has been advocated to unmask proarrhythmic potentials in patients receiving flecainide acetate, the effects of this drug on exercise parameters in individuals without structural heart disease have not been reported. This study was undertaken to assess the effects of flecainide on hemodynamics and electrocardiographic changes during exercise testing in 24 patients with paroxysmal supraventricular tachyarrhythmias, who had normal cardiac structure and sinus node function. Paired treadmill exercise tests using the Bruce protocol were performed after 1 week of treatment with flecainide (200 mg/day) or placebo in a double-blind, randomized design. Exercise testing was terminated because of either fatigue or dyspnea in all subjects. Although resting heart rate was unaffected, flecainide reduced the exercise heart rate (expressed as a percentage of age-predicted maximum) compared with placebo (84 +/- 12% vs. 92 +/- 9%, p < 0.001). Neither resting and exercise systolic blood pressure nor exercise duration were affected. PR interval shortening with exercise was not affected by flecainide, whereas QRS was prolonged compared with placebo (20 +/- 9% vs. 0 +/- 8%, p < 0.01). Compared with placebo, flecainide significantly shortened QTc (-7 +/- 12% vs. 0 +/- 8%, p < 0.05) and JTc (-34 +/- 11% vs. -21 +/- 11%, p < 0.01) intervals during exercise. During exercise, flecainide produced significant depression in the sinus node automaticity and manifested use-dependent slowing of ventricular conduction and acceleration in ventricular repolarization.