In a prospective randomized study, we assessed the electrophysiologic effects and the efficacy of ajmaline versus propafenone in patients with accessory pathways (APs). During initiated atrioventricular (AV) reentrant tachycardia or atrial fibrillation (AF), ajmaline (1 mg/kg as bolus followed by infusion of 15 micrograms/kg/min) or propafenone (2 mg/kg, followed by infusion of 30 micrograms/kg/min.) were randomly administered intravenously (i.v.) in 40 patients with APs. AV reentrant tachycardia terminated in 15 of 16 patients (94%) on ajmaline and in 12 of 15 patients (80%, NS) on propafenone. AF ceased in 4 of 4 patients receiving ajmaline and in 3 of 5 patients receiving propafenone (n.s.). During continuous infusion of drugs, AV reentrant tachycardia became noninducible in 10 (50%) patients receiving ajmaline, as compared with 6 (32%) receiving propafenone (NS). Both drugs significantly prolonged the anterograde and retrograde effective refractory periods (ERPs) of the AP. There were no significant differences in changes in electrophysiologic parameters between the two drugs. Ajmaline and propafenone are highly effective and safe in terminating and preventing reinitiation of AV reentrant tachycardia or AF in patients with APs. Both drugs significantly prolonged the anterograde and retrograde ERPs of the APs.