This study was undertaken to evaluate the effect of flecainie (Fle) and propafenone (Pro) on rest and exercise myocardial contractility after prolonged oral administration. Standardized, fully automated, gated radionuclide angiograms at rest and during maximum exercise were performed single blinded and prospectively in 19 patients before and after oral treatment with either 150 mg b.i.d. of Fle or 150 mg t.i.d. of Pro. The left ventricular ejection fraction (EF%) as a hemodynamic indicator presented as follows: (Table: see text) In general, there was no significant effect of either drug on resting ventricular function. In only one patient of the Fle group with decreased baseline function did the left ventricular EF fall from 40% to 29%. During exercise, ventricular performance showed deterioration in the Pro group, but, interestingly, improvement in the Fle group. As a result of these opposite changes, the effect of the two drugs on the exercise response of ventricular function was significantly different (P less than 0.05). This study thus gives first evidence that no significant cardiodepressive effects are to be expected after prolonged application of Fle or Pro in normal hearts. There might even be a mild beneficial effect on exercise performance after Fle.