Abstract Flecainide has unusual electrophysiologic properties and a high potency for the suppression of ventricular tachyarrhythmias. Little is known about its inotropic and hemodynamic actions. In isolated rabbit papillary muscle, it produced a concentration-dependent depression of contractile force, the threshold concentration being 1.0 μg/ml. In patients undergoing coronary angiography for ischemic heart disease and given 1 (n = 11) and 2 mg/kg (n = 11) of flecainide acetate i.v., there was no change in heart rate or mean arterial pressure. The vehicle in which i.v. flecainide was suspended had no significant effects in 6 patients in whom it was tested. Both doses produced comparable hemodynamic effects irrespective of the level of the left ventricular ejection fraction. The mean right atrial pressure increased by 12% (p < 0.05) after 1 mg/kg and by 15% (p < 0.01) after 2 mg/kg of the drug. The corresponding increases in mean wedge pressure were 44% (p < 0.05) and 33% (p < 0.05), in mean pulmonary artery pressure 27% (p < 0.01) and 28% (p < 0.05), in systemic vascular resistance 10% (p < 0.05) and 9% (not significant [NS]) and in pulmonary vascular resistance 6% (NS) and 49% (p < 0.05). Significant decreases in cardiac index (8 and 12%, p < 0.05), stroke volume index (11 and 15%, p < 0.01) and stroke work index (12%, p < 0.05, and 21%, p < 0.01) as well as in left ventricular ejection fraction (15 and 16%, p < 0.01) were also induced by the 2 doses of flecainide. In 373 patients (67 with a history of cardiac failure) given doses of flecainide to control ventricular tachyarrhythmias, heart failure developed or was aggravated in 16, an incidence of 4.3%. The overall data indicate that flecainide exhibits significant but modest negative inotropic effects that may become clinically significant in the subset of patients with compromised ventricular function. Its use in patients with severely depressed myocardial function warrants caution.