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Recent technologic advances make it possible to measure reliably serum or plasma ionized calcium with a high degree of accuracy. In this study, with the use of 16 mongrel dogs, the quantitation of the hemodynamic response to acute changes in ionized calcium was attempted. It was found that normal cardiac function required a normal level of ionized calcium. In intact animals, severe depression of myocardium is masked by pressor reflexes designed to maintain homeostasis. In their absence, myocardial depression is readily apparent. Animals that are hypercalcemic at the beginning of infusion respond in essentially the same manner. To a degree previously unsuspected, myocardial function depends upon a constant level of ionized calcium.