The effects of lidocaine and methyl lidocaine on cardiac conduction were studied using His bundle recordings from isolated blood perfused dog hearts. The input and output characteristic of the atrioventricular (AV) node can be described as consisting of three components, namely, minimal conduction time, fatigue, and the effect of prematurity (deltaCT). Lidocaine (2.5-10.0 mg/kg) increased minimal conduction time but not fatigue. Methyl lidocaine (1.25-5.0 mg/kg) increased both. A dose of 5 mg/kg or less of either drug caused a nonparallel shift of the deltaCT curve to the right. High doses of lidocaine (10 mg/kg) cause deltaCT to become rate-dependent. Lidocaine slowed atrial conduction only slightly. Atrial block prevented the observation of the effect of methyl lidocaine in doses higher than 5.0 mg/kg. Both drugs showed greater effect on atrial conduction at fast heart rate. Lidocaine did not affect ventricular conduction time at slow heart rates and had only minimal effects at fast heart rates. Methyl lidocaine increased ventricular conduction time at all heart rates. The results of this study indicate that lidocaine and methyl lidocaine have entirely different spectra of activity on cardiac conduction, in that their effect on AV nodal conduction do not differ greatly whereas the quaternary analog has a much stronger depressant effect on atrial and ventricular conduction.