Cell death secondary to transient myocardial ischemia occurs mainly as necrosis during the first minutes of reperfusion. Post- reperfusion infarcts are formed by areas of contraction band necrosis composed of hypercontracted myocytes. The importance of hypercontracture as a causative mechanism of cardiomyocyte death during reperfusion has been consistently demonstrated by studies showing that transient contractile blockade at the onset of reperfusion effectively prevents cell death. Contractile activation secondary to resumption of ATP synthesis in the presence of high cytosolic Ca2+ is the main determinant of reperfusion-induced hypercontracture. On the other hand, recent studies suggest that a sudden change in the permeability of the mitochondrial membranes by opening of a high conductance pore (mitochondrial permeability transition pore (mPTP)) may play a causative role in post-reperfusion necrotic death of cardiac myocytes by arresting mitochondrial respiration. A prominent role of mPTP opening in reperfusion-induced myocardial necrosis is difficult to reconcile with a causative role of energy-dependent hypercontracture. Here, we tested the hypothesis of a cause-effect relationship between opening of mPTP and hypercontracture. Energetic recovery, hypercontracture, Ca2+ concentrations, and mPTP opening were monitored in isolated cardiomyocytes and