The alterations in the ultrastructure of the isolated perfused Rana ridibunda hearts that were subjected to prolonged calcium depletion and reperfusion with calcium containing medium are described using thin section electron microscopy. Deprivation of calcium resulted in broadened intercellular spaces and in mild cell swelling. Cell to cell contact was maintained throughout calcium depletion, while myofibrils and mitochondria remained intact. Reintroduction of calcium containing buffers to calcium depleted hearts resulted in an irreversible injury of the frog myocardial cells. The main characteristics of the reperfusion induced damage were contraction band formation, distortion and degradation of the myofibrils, extensive swelling of the mitochondria and formation of intramitochondrial electron dense deposits. Mitochondrial aggregation, intermitochondrial junctions, expulsion of the mitochondria to the sarcolemmal membrane and peripheral condensation of nuclear chromatin were also observed. Our results indicate that frog myocardial cells show a marked resistance even to a prolonged calcium depletion, retaining their integrity and their contact. However, the following reperfusion greatly alters the ultrastructure of frog myocardium and the observed alterations are typical of the irreversible damage induced in calcium overload situations.