Although adenosine depresses antegrade atrioventricular (AV) nodal conduction, the effects of adenosine on antegrade and retrograde fast pathway conduction in AV nodal reentry have not been determined. In 17 patients (five men, 12 women, mean age 49±12 years) with common slow-fast AV nodal reentrant tachycardia, the antegrade slow pathway conduction was selectively and completely ablated by radiofrequency catheter ablation while the antegrade and retrograde fast pathway conduction remained intact. During high right atrial pacing at a mean pacing cycle length of 474±36 msec, adenosine was rapidly injected intravenously at an initial dose of 0.5 mg followed by stepwise increases of 0.5 mg or 1.0 mg given at 5-minute intervals until second-degree AV block developed. During right ventricular apical pacing at the same pacing cycle lengths (mean 474±36 msec) as those in the study of antegrade conduction, intravenous injection of incremental doses of adenosine was repeated until ventriculoatrial (VA) block occurred. The adenosine-induced prolongation of VA conduction was also determined in the presence of verapamil (loading dose 0.15 mg/kg, maintenance dose 0.005 mg/kg/min) in seven of 17 patients. The dose of adenosine required to produce AV block, the increase in the atrio-His interval by 50% and the maximal response were 3.4±1.4 mg, 1.8±0.6 mg, and 58%±5%, respectively. On the other hand, the dose of adenosine required to produce VA block, the increase in the VA interval by 50%, and the maximal response were 8.2±2.9 mg, 3.4±0.6 mg, and 20%±5%, respectively, in the control and 3.7±0.5 mg, 3.5±0.7 mg, and 23%±5%, respectively, in the presence of verapamil. In conclusion, adenosine has a differential potency to depress AV and VA conduction in patients with AV nodal reentry, with greater potency for slowing antegrade fast than retrograde fast pathway conduction. Verapamil had an additive effect to adenosine on slowing retrograde VA conduction, which further supports the evidence that the retrograde fast pathway in part involves an AV nodal-like structure.