The cardiac electrophysiology of flecainide, a new antiarrhythmic agent, was studied in open-chested dogs. At plasma concentrations of 0.4 to 0.7 μg/ml. flecainide significantly prolonged atrioventricular (AV) conduction. At plasma concentrations greater than 6.5 μg/ml, flecainide caused delay throughout the conduction system (77–240%). Low plasma levels of flecainide caused slight prolongation in atrial effective refractory period and AV nodal functional and relative refractory periods. At flecainide levels of 0.7 μg/ml, ventricular response during atrial fibrillation was significantly slowed. The effects of flecainide on AV nodal and infranodal conduction and refractoriness were significantly enhanced by d, l-propranolol (0.5 mg/kg) but were unaffected by ouabain (0.01 mg/kg). The ventricular fibrillation threshold of supraventricular beats and ventricular premature beats increased with increasing plasma flecainide concentration (122% at 9.3 μ/ml and 172% at 1.3 μg/ml, respectively). Flecainide slowed ectopic atrial and ventricular pacemakers without affecting sinus or junctional pacemakers.