During ischemia, lidocaine or quinidine may prevent arrhythmias by blocking conduction without suppressing abnormal automaticity. The purpose of this study was to determine whether lidocaine or quinidine (5 micrograms/ml) produced Purkinje fiber-papillary muscle block during superfusion in vitro with an altered Tyrode's solution containing some components of ischemia: 6 mM potassium, PO2 less than 40, pH = 6.8. Unbranched canine Purkinje fibers connected to papillary muscle at one end were threaded through a three-chamber bath with Purkinje fiber-papillary muscle in the left chamber and Purkinje fiber alone in the middle and right chambers. Action potentials were recorded using microelectrodes from Purkinje fiber, papillary muscle, and cells at the Purkinje fiber-papillary muscle junction. Purkinje fiber or papillary muscle was stimulated at 1.5-4 Hz. Perfusion of the left chamber with altered Tyrode's solution decreased resting membrane potential, action potential amplitude, and the maximum rate of rise of phase 0 of the action potential of Purkinje fiber, papillary muscle, and junctional cells, and prolonged activation times of junctional cells and papillary muscle; but action potentials propagated from Purkinje fiber to papillary muscle, and from papillary muscle to Purkinje fiber. Lidocaine or quinidine plus altered Tyrode's solution further decreased action potential amplitude and the maximum rate of rise of phase 0 of the action potential of Purkinje fiber, papillary muscle, and junctional cells, and prolonged activation of junctional cells and papillary muscle, inducing bidirectional block only at the Purkinje fiber-papillary muscle junction. Lidocaine or quinidine plus normal Tyrode's solution and each component of altered Tyrode's solution alone did not produce block. Perfusion of the right chamber with 0.25 mM barium induced Purkinje fiber automaticity that: propagated to papillary muscle during perfusion of the left chamber with normal Tyrode's or altered Tyrode's solution; blocked at the Purkinje fiber-papillary muscle junction during perfusion of the left chamber with altered Tyrode's solution plus lidocaine; and was not suppressed during perfusion of the right chamber with lidocaine. Thus, lidocaine or quinidine may produce bidirectional block at Purkinje fiber-papillary muscle junction and interrupt a potential limb of a reentrant circuit without suppressing automatic arrhythmogenic foci.