The electrophysiological effects of imipramine (Tofranil) on cardiac Purkinje fibers were studied in vitro. Imipramine has a direct membrane action. It reduces excitatory inward current in Purkinje fibers, at least as measured by Vmax and conduction velocity. The mechanism of action of imipramine is probably by both reduction in gNa and marked slowing of the time constants of recovery of the rapid inward sodium current. Imipramine also reduces the action protential duration, decreasing the absolute refractory period. This effect is not seen with antiarrhythmic agents of the local anesthetic class, but it is similar to lidocaine. This effect may be a result of the decrease in steady-state gNa, but effects of the drug on other ionic conductances could play a role.