Verapamil is used to control ventricular response during atrial fibrillation (AF). Limited data is available on the effects of verapamil on atrial vulnerability in human AF. The effects of intravenous verapamil (0.15 mg/kg) on electrophysiological properties of the atrium were investigated in 12 patients with documented paroxysmal AF by electrophysiological studies. Sinus cycle length, sinus node recovery time, and the effective refractory period of the right atrium were not significantly affected by verapamil. The intraatrial conduction delay zone was significantly increased (33 +/- 20 msec before verapamil versus 50 +/- 22 msec after verapamil, P < 0.01), and the maximal intraatrial conduction delay was also significantly prolonged by verapamil, both to the His bundle region (30 +/- 12 msec before verapamil versus 42 +/- 15 msec after verapamil, P < 0.01) and to the coronary sinus (40 +/- 15 msec before verapamil versus 53 +/- 17 msec after verapamil, P < 0.01). The fragmented atrial activity zone was significantly increased (15 +/- 14 msec before verapamil versus 25 +/- 22 msec after verapamil, P < 0.02), and the percentile fragmented atrial activity was also significantly increased by verapamil (149 +/- 18 msec before verapamil versus 174 +/- 44 msec after verapamil, P < 0.05). The repetitive atrial firing zone remained unchanged. Sustained AF spontaneously occurred in only one patient after the administration of verapamil. Thus, verapamil may modulate the abnormal atrial electrophysiology in paroxysmal AF, and would favor production of atrial reentry.