We studied the effects of the local anesthetics, procaine and benzocaine, on the action potential and force of canine ventricular muscle and Purkinje fibers. In ventricular muscle, procaine often shifted the plateau to a more positive value and increased the force of contraction, whereas benzocaine shortened the action potential and decreased contractile force. In Purkinje fibers, both local anesthetics reduced contractile force and decreased the duration of the action potential markedly. In ventricular muscle fibers norepinephrine potentiated the positive inotropic effect of procaine and changed the effects of benzocaine from a negative to a positive inotropic effect. The potentiating effect of procaine on contraction was eliminated by propranolol. In the presence of norepinephrine (and the absence of propranolol), in Purkinje fibers both anesthetics decreased force but less than in the absence of norepinephrine. In the presence of tetrodotoxin (TTX) and norepinephrine, procaine and benzocaine increased contractile force of muscle fibers. Under the same conditions in Purkinje fibers, procaine increased contractile force and benzocaine decreased it (but less than in the absence of TTX). Admin-istration of veratridine increased contractile force in both ventricular muscle and Purkinje fibers: under these conditions, both local anesthetics decreased contractile force in both tissues. We conclude that: (1) the positive inotropic effects of procaine and benzocaine are mediated through an adrenergic mechanism; (2) the negative inotropic effect is at least in part mediated through a reduction of sodium influx; and (3) the negative inotropic effect is more pronounced in Purkinje fibers because of a larger steady state sodium influx during the plateau.Circ Res 47: 666-674, 1980