Under physiological conditions different parts of the heart reveal superspecialization of the myocardium reflected by biochemical, functional, structural and histochemical differences, which are even more pronounced under pathological conditions. Postischemic reperfusion, Ca paradox and injury caused by reactive oxygen species were found to result in transmurally unhomogenous damage of the ventricular wall. In the present experiments isolated perfused rat hearts were subjected to damage by the above mechanism and a different vulnerability of defined parts of the heart was observed. Activities of glycogen phosphorylase, SDH, beta-HBDH, and LDH were studied histochemically in both ventricles, the atria and the specialized conductive system of the heart. Marked decreases of activities were observed in the ventricular muscle. The enzyme activities were less decreased in the atrial muscle. Conductive fibres were the least affected tissue in this respect. The differential changes were most sensitively reflected by glycogen phosphorylase. The differences in transmural distribution of damage were shown to be dependent on a complex of specific factors such as intramural pressure gradient, transmural pressure, end-diastolic intraventricular pressure, differences in transmural vessel distribution, transmural hematocrit differences, blood flow, perfusate volume, and endothelial injuries of different origin. It can be concluded that differences in ultrastructure as well as in enzyme activities in different parts of the heart reflect functional, structural and metabolic heterogeneity of the different functional parts of the heart muscle.