The hypothesis that human atrioventricular (AV) nodal function can be modulated selectively with a new technique of AV nodal artery catheterization was tested in eight subjects referred for diagnostic cardiac catheterization or electrophysiological studies. Three patients had no history of arrhythmias. Three patients had supraventricular tachycardia (SVT) due to reentry confined to the AV node (AVNRT). One patient had SVT due to reentry over a concealed AV bypass tract (AVRT-CBT), and one patient had nonsustained ventricular tachycardia. In each subject, sinus cycle length, AH interval, HV interval, AV nodal effective refractory period (AVN-ERP), and Wenckebach paced cycle length were measured in a control state. A flexible infusion catheter was then positioned selectively in the AV nodal artery of each subject. Through this catheter, a constant infusion of 0.1 mg/min procainamide at a flow rate of 0.125 ml/min (n = 1) or 50 micrograms/min acetylcholine at a flow rate of 0.25 ml/min (n = 4) was administered. Electrophysiological parameters were determined again during selective AV nodal artery drug infusion and during infusion of saline at identical rates. Two subjects developed transient AV nodal block during selective AV nodal catheterization alone and did not receive an infusion of drug or saline. A stable position of the AV nodal artery catheter could not be achieved in one other subject, who also received no drug or saline. In the other five subjects, drug infusion caused an increase in AVN-ERP from a control value of 312 +/- 52 msec to a value of 543 +/- 228 msec (p less than 0.05) and an increase in Wenckebach paced cycle length from a control value of 360 +/- 47 msec to a value of 572 +/- 217 msec (p less than 0.05). These parameters were unchanged from control during selective saline infusion. In two patients with AVNRT, drug infusion abolished SVT by causing complete blockade of ventriculoatrial conduction as well as lengthening of anterograde AVN-ERP. In the patient with AVRT-CBT, drug infusion abolished SVT by preventing repetitive anterograde AV conduction. Saline had no effect on SVT inducibility. Selective AV nodal artery catheterization enables AV nodal function to be modulated exclusively. Delivery of ablative agents to the AV node by this technique may be useful in patients with refractory SVT.