The effect of restacorin (5 microM) and flecainide (5 microM) on the transmembrane ionic currents was compared in dog and rabbit ventricular muscle by applying the conventional microelectrode and patch-clamp techniques. Neither restacorin nor flecainide influenced significantly the ATP-sensitive and inward rectifier potassium currents. Flecainide moderately decreased the amplitude of the transient outward current while restacorin did not change this current. The delayed rectifier potassium current was depressed markedly by flecainide and moderately by restacorin. These results suggest that although flecainide and restacorin cause similar changes in the various transmembrane ionic currents, there are some differences between the effects of the two antiarrhythmic compounds.