Studies were carried out in rats on myocardial adaptation to injury produced by left coronary artery ligation. In the ischemic zone, open collaterals were present as shown by studies using the fine structural extracellular protein tracer, horseradish peroxidase (HRP). This phenomenon may explain the inhomogeneous cardiac muscle cell alteration in the early phase of coronarogenic myocardial injury. Reperfusion, as evidenced by the influx of HRP into the damaged cells, unmasked sarcolemmal membrane injury. Cardiac muscle cell stimulation modifies the binding of macromolecules to cell components and may influence the repair processes. In the surviving myocardium, correlative enzyme histochemical and ultrastructural studies demonstrated the development of alternative metabolic pathways and morphological signs of adaptation explaining increasing resistance of such cardiac muscle cells to subsequent insult.