The removal of Ca²⁺ from the cardioplegic solutions could cause the danger of inducing a "calcium paradox" during reperfusion. Since intracellular Ca²⁺ activities are coupled to Na⁺ activities via Na(+)-Ca²⁺ exchange, an increase in intracellular Na⁺ activities during the cardioplegia could cause an abrupt Ca²⁺ influx when reperfused. To study the effects of Na⁺ and Ca²⁺ concentrations in cardioplegic solutions on intracellular Ca²⁺ activities during the cardioplegia and subsequent recovery period, the membrane potential and intracellular Na⁺ and Ca²⁺ activities of guinea pig ventricular papillary were measured. 1) A cardioplegia with low Ca²⁺ cardioplegic solution significantly decreased the overshoot and duration of the first action potential after cardioplegia, but the changes in action potential configuration were minimized after a cardioplegia with Ca²⁺ concentration adjusted according to the Na(+)-Ca²⁺ exchange mechanism. 2) Intracellular Na⁺ activity was continuously decreased during the cardioplegia, and the intracellular Na⁺ activity 20 minutes after cardioplegia was the highest with low Ca²⁺ cardioplegic solution. 3) Intracellular Na⁺ and Ca²⁺ activities were continuously decreased during the cardioplegia with Ca²⁺ concentration adjusted according to the Na(+)-Ca²⁺ exchange mechanism. 4) During a reperfusion of Tyrode solution after cardioplegia intracellular Na⁺ and Ca²⁺ activities were increased. Intracellular Ca²⁺ activity was increased more rapidly than intracellular Na⁺ activity. 5) The rate of increase in intracellular Ca²⁺ activity with reperfusion of Tyrode solution was dependent upon intracellular Na⁺ activity during cardioplegia, in such a way that the higher the intracellular Na⁺ activity was, the faster the intracellular Ca²⁺ activity increased. These data suggest that Na(+)-Ca²⁺ exchange mechanism may play an important role in the regulation of intracellular Ca²⁺ activity during recovery after cardioplegia.