The antiarrhythmic activity of flecainide acetate (R-818), 2 mg/kg, was investigated in anesthetized, open-chest pigs. Ventricular arrhythmias were provoked by reducing the flow in the left anterior descending coronary artery (LAD) to 25% of control during 30 min. During this period ventricular fibrillation occurred in 33% (11 out of 33) of control animals against 12.5% (1 out of 8) of animals treated with flecainide. Ventricular tachycardias were seen in 42% (14 out of 33) of the untreated animals as compared to none of the animals previously treated with flecainide. Total number of ventricular arrhythmias was significantly lower in the treated than in the untreated animals (p < 0.05). However, when the LAD was occluded completely at its distal part, ventricular fibrillation occurred in all animals (5 untreated and 6 pretreated with flecainide). Time to onset of ventricular fibrillation was the same for both groups of animals, despite a lower incidence of preceding ventricular arrhythmias in the pretreated group. Flecainide depressed myocardial contractility (LV dP/dt max), caused hypotension, and increased QRS width. Both myocardial depression and widening of QRS are related to arterial plasma levels of flecainide. Therefore, a slower infusion rate than the 1 mg/kg per minute used in this study is advisable when myocardial function is impaired.