Precise effects of antiarrhythmic drugs (AAD) on the human atrial flutter (AFL) circuit are unknown. We study the effects of propafenone (PRO) and amiodarone (AMI) on the right atrial isthmus (IS) and free wall (FW) in 24 patients (pts) with typical AFL (Group I) and 20 pts without AFL (Group II). A 20-pole Halo catheter was placed around the tricuspid anulus. Incremental pacing from the low lateral right atrium was performed to measure conduction velocity (CV) along the IS and FW, and atrial extrastimulation was used to determine the effective refractory period (ERP) of the IS and FW before and after infusion of PRO and AMI.Results: IS-CV and FW-CV were greater in Group II than in Group I. PRO decrease IS-CV leading to greater increase of AFL cycle length (62 +/- 12 vs 8 +/- 6%) and termination (66 vs 33%) of AFL, but AMI did not significantly change IS-CV or FW-CV. PRO prolonged IS (26 vs 12%) and FW (29 vs 11%) ERPs with greater extent than AMI.Conclusions: (1) IS had lower CV than FW in pts with or without AFL. (2) PRO had differential effects on IS and FW during atrial pacing and AFL. (3) Slowing of IS-CV with conduction block may be critical to termination of AFL by AAD.