Atrial fibrillation is one of the most commonly encountered clinical arrhythmias. Different treatment options for this rhythm disorder exist with the electrical and/or pharmacological cardioversion to sinus rhythm with subsequent antiarrhythmic drug therapy to prevent recurrences being one of the primary therapeutic goals. Another alternative, however, is represented by the control of the ventricular rate in patients with persistent atrial fibrillation. The question of which these two strategies should be preferred in the majority of patients with atrial fibrillation has not been studied in a prospective way. Given the background of conflicting data with respect to the prognostic impact of atrial fibrillation and of the increasing evidence concerning the risks of antiarrhythmic drug treatment in atrial fibrillation, a prospective multicenter trial has been initiated to compare these two therapeutic alternatives prospectively. Patients will be randomly assigned to cardioversion with subsequent antiarrhythmic drug therapy to prevent recurrent atrial fibrillation or to a therapy aiming exclusively at control of the ventricular rate during persistent atrial fibrillation. All patients will receive anticoagulation by means of warfarin (target INR 2.5-3.5) to prevent thromboembolic complications. The rationale and the design of the PIAF trial (Pharmacological intervention in Atrial Fibrillation) are discussed below. The pilot phase of this study has begun patient enrollment in the spring of 1995.