Flecainide and verapamil are antiarrhythmic agents that may be used in combination. We have examined their pharmacodynamic interaction by M-mode echocardiography and electrocardiography in eight normal male volunteers (24 ± 1.8 years of age). Flecainide decreased the left ventricular ejection fraction (LVEF) (-4.4 ± 1.2%, p < 0.008), but verapamil did not. Neither drug affected cardiac output or vascular resistance. Both drugs increased the PR interval (12 ± 4 msec, p < 0.01 for flecainide; 12 ± 5, p < 0.04 for verapamil). Flecainide, but not verapamil, increased the QTc interval (23 ± 8 msec, p < 0.02). Both drugs also increased the systolic time interval ratio (PEPc/LVETc)(0.074 ± 0.012, p < 0.0004 for flecainide; 0.029 ± 0.008, p < 0.007 for verapamil). The combination of flecainide and verapamil had additive effects on myocardial contractility and on atrioventricular conduction. Verapamil slightly decreased the plasma clearance of flecainide (7.78 ± 0.60 ml/kg/min for flecainide alone, 7.34 ± 0.48 ml/kg/min for flecainide and verapamil together, p < 0.05). On the other hand, flecainide had no effect on the plasma clearance of verapamil, which suggests that there was little interaction between the two drugs on their pharmacokinetic parameters.