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The effects of different extracellular calcium concentrations on the changes in myocardial Ca2+ content ([Ca2+]m), ultrastructure, and contractile force (CF) associated with the calcium paradox phenomenon were examined in isolated perfused rat hearts. In the first series of experiments, the hearts were perfused for 5 min with various calcium concentrations (0, 0.025, 0.05, 0.1, 0.25, 0.5, 1.25 mM) followed by 5 min of reperfusion with normal medium (1.25 mM Ca2+). Reperfusion-induced changes in the above parameters were prevented if the calcium concentration was 0.1 mM or higher. Reducing the calcium concentration to 0.05 mM or less resulted in an increase in [Ca2+]m and partial or no recovery of CF upon reperfusion. In the second series of experiments, hearts perfused for 5 min with Ca2+-free medium were reperfused for 5 min with different calcium concentrations (0.025, 0.05, 0.1, 0.25, 0.5, 1.0, 1.25, 2.5, 4.0 mM). Reperfusion-induced increases in [Ca2+]m, the degree of contracture, and ultrastructural damage were dependent upon the external calcium concentration. A sevenfold increase in [Ca2+]m, loss of cell-to-cell contacts, disruption and loss of mitochondria, and poor definition of A and I bands were observed after reperfusion with 4 mM Ca2+. The changes observed appear to be associated with the extent of calcium overload and are related to the extracellular calcium concentration.