Summary The new antiarrhythmic drug flecainide (2,5-bis-(2,2,2-trifluoroethoxy)-N-(2-piperidylmethyl) benzamide acetate) increases action potential duration at 30 and 90% repolarization, and functional refractory period in guinea pig papillary muscle up to 10 μmol/L, but shortens the action potential and decreases its amplitude at 30 μmol/L, without significant change in resting potential. 10 μmol/L flecainide decreases maximal upstroke velocity (max) by about 40% at a stimulation rate of 1 Hz, whereas at 0.017 Hz max remains nearly unchanged (use-dependence). Flecainide delays recovery from inactivation of the fast-sodium channels. Its potential-dependent action on max is demonstrated by a shift to more negative potentials of the membrane responsiveness curve and of the curve that relates membrane potential to max in K+-depolarized papillary muscles driven at 0.017 Hz (hx-curve). Flecainide increases threshold of alternating current-induced arrhythmia and asystole in left atria and papillary muscles to a similar extent, and in this respect resembles the local anesthetics. Force of contraction of atrial and ventricular myocardium is significantly decreased at ≥10 μmol/L flecainide, and frequency of spontaneously beating right atria at ≥0.3 μmol/L. The results indicate that the predominant action of flecainide consists of a potent inhibition of cardiac fast sodium channels.