Instrastimulus Polarity Reversal. Introduction: This study investigated the effect of introducing one or two intrastimulus polarity reversals during an electric field stimulus pulse (S2) on the ability of the stimulus to excite frog ventricular strips and rabbit papillary muscles. Methods and Results: Excitation thresholds were determined with normal extracellular [K] and an S1 pacing rate of 0.5 Hz (control), after increasing the [K] or after 20 seconds of S1 pacing at 5 Hz. For S2 having durations of 1.5 or 3 msec under control conditions, the incorporation of one intrastimulus polarity reversal increased thresholds by 93% or 50%, respectively, while the incorporation of two reversals increased thresholds by 170% or 110%. For S2 having a duration of 20 msec, reversals had little effect under control conditions. When the muscle was driven at an S1 rate of 5 Hz for 20 seconds or when the extracellular [K] was increased to 10.6 mM, interventions that depolarized the resting membrane potential approximately 8 to 15 mV, the incorporation of one intrastimulus polarity reversal increased the threshold for 3-msec S2 nearly as much as it did under control conditions but, unlike control, the reversal decreased the rheobase of the Lapicque relation for the strength-duration curve for S2 by 17% to 36%. Intracellular and interstitial recordings indicated a time dependence of the hyperpolarization and depolarization in the muscles during S2 consistent with the membrane capacitance. The results support two competing effects of intrastimulus polarity reversal during electric field stimulation: (1) decreased ability to excite due to a decrease in the time available to discharge the membrane capacitance to the transmembrane threshold potential; and (2) increased ability to excite due to restoration of inactivated voltage-dependent inward sodium channels in the part of the membrane that is hyperpolarized before a reversal. Conclusion: Thus for an electric field stimulus with a duration < 12 msec, intrastimulus polarity reversals decrease the ability to excite ventricular muscle. With a duration > 20 msec and under conditions that depolarize the resting membrane potential, one intrastimulus polarity reversal increases the ability of an electric field stimulus to excite ventricular muscle.