The effect of calcium-free reperfusion for 5, 10, and 15 minutes, respectively, followed by continuous reperfusion with normal Tyrode solution containing 1.0mM calcium chloride, after global ischemia in the isolated perfused guinea pig heart by Langendorff techniques was examined with transmission electron microscope. Compared to the nomal Tyrode solution-perfused control hearts, the 5 minute calcium-free-reperfused hearts showed loss or thickening of Z lines, focal sarcolemmal disruption, mitochondrial swelling, clumping of chroma-tin, intracellular fluid accumulation, and some separation of cell junctions, especially the fasciae adherentes. These changes became more severe in the hearts of 10 minute calcium-free reperfusion. Subsarcolemmal larger bleb and near complete separation of cell junctions were noticed. In the 15 minute calcium-free-reperfused hearts, irreversible ultrastructural changes including contraction bands, biazrre mitochondria, and sarcolemmal destruction were widely distributed. The severity of myocardial changes were in accordance with the duration of calcium-free reperfusion. These changes indicate that calcium-free reperfusion regardless of its duration could not salvage the post-ischemic myocardium probably due to development of calcium paradox.