Programmed electrical stimulation (PES) was used to compare the effects of flecainide and D-sotalol in a canine occlusion-reperfusion infarction model. The increase in the effective refractory period (ERP) was greater with D-sotalol than with flecainide (26.4 +/- 5.2 vs. 10.3 +/- 2.7 ms). In contrast, ventricular activation time was significantly increased by flecainide (from 72 +/- 2 to 87 +/- 3 ms) but was unchanged after D-sotalol administration (from 73 +/- 2 to 75 +/- 2 ms). Thirteen dogs with inducible sustained ventricular arrhythmias at control became noninducible after drug administration. All but one of these favorable drug responses were associated with D-sotalol. In contrast, 10 noninducible dogs at control had sustained ventricular arrhythmias induced after drug administration. All of these adverse responses were associated with flecainide (p < 0.0001). An increase in the ratio of conduction to refractoriness was observed in 100% of adverse drug trials but in only 25% of favorable drug trials (p = 0.003). These data suggest that flecainide enhances induction of sustained ventricular arrhythmias in this postinfarction canine model. This proarrhythmic drug effect may be related to the selective effect of flecainide on myocardial conduction.