Cardiac dysfunctions such as myocardial functional failure and ventricular arrhythmia have been largely attributed to intracellular Ca²⁺ overload. One of the mechanisms of intracellular Ca²⁺ overload involves a rapid influx of Ca²⁺ via Na⁺-Ca²⁺ exchange during the reperfusion which utilizes the accumulation of Na⁺ in myocytes during ischemic cardiac arrest. Possible sources of the intracellular Na⁺ accumulation include Na⁺ channel, Na⁺-H⁺ exchange, Na⁺-Ca²⁺ exchange, and Na⁺ background current. In this study, we studied the role of the Na⁺ background current in intracellular Na⁺ accumulation during the cardiac arrest by measuring the Na⁺ background current in guinea pig ventricular myocytes with whole cell clamp method and evaluating the effects of cardioprotective drugs on the Na⁺ background current. The results were as follows: (1) The Na⁺ background inward current at -40 mV membrane potential was larger at Ca²⁺ free solution than 1.8 mM Ca²⁺ solution. (2) The Na⁺ background current was not affected by verapamil. (3) 2 µM O-(N, N-hexamethylene)-amiloride (HMA) decreased the Na⁺ background current at negative membrane potential. (4) The new cardioprotective drug, R 56865, decreased the Na⁺ background current. These results suggest that the Na⁺ background current plays a role in increasing the intracellular Na⁺ activity during high K⁺ cardioplegia and the blocking effect of myoprotective drugs, such as R 56865, on the Na⁺ background current may contribute to myocardial protection after cardioplegia.