The inferior atrial extensions of the atrioventricular (AV) node have been related to the anatomic substrate of the slow pathway, but their role in AV nodal reentrant tachycardia (AVNRT) is unknown. Ten patients with slow-fast AVNRT were studied before and after successful slow pathway ablation. Simultaneous His bundle recordings from the right and left sides of the septum were made during right and left inferoparaseptal pacing. Longer stimulus to His (St-H) intervals were measured during right inferoparaseptal pacing than during left inferoparaseptal pacing (284 +/- 55 vs 246 +/- 46 ms, p = 0.005 for right His recordings and 283 +/- 56 vs 244 +/- 46 ms, p = 0.005 for left His recordings) at similar coupling intervals during AVNRT induction. After ablation, the St-H intervals at the maximum AV nodal conduction decrement were similar during right inferoparaseptal and left inferoparaseptal pacing (217 +/- 32 vs 207 +/- 21 ms, p = 0.10 for right His and 215 +/- 32 vs 206 +/- 20 ms, p = 0.13 for left His) at similar coupling intervals. The difference (DeltaSt-H) between St-H intervals during AVRNT induction or at the maximum conduction decrement and during constant pacing for right His recordings with right inferoparaseptal pacing were significantly greater than DeltaSt-H measured with left His during left inferoparaseptal pacing (173 +/- 64 vs 137 +/- 55 ms, p = 0.005) before ablation, but not after (117 +/- 39 vs 100 +/- 40 ms, p = 0.44). Resetting of AVNRT with delivery of left inferoparaseptal extrastimuli was achieved in 7 of 10 patients. In conclusion, the electrophysiologic characteristics of the right and left inferior atrial inputs to the human AV node in patients with AVNRT and their response to slow pathway ablation provide further evidence that the inferior nodal extensions represent the anatomic substrate of the slow pathway.