Ventricular contracture was produced in isolated perfused rat hearts by a novel method using repeated administration of an anoxic cold hyperkalemic cardioplegia solution. Contracture could be reversed by reperfusion with the same solution, without calcium (Group 1), oxygenated (Group 2), or oxygenated and calcium free (Group 3). Group 1 hearts underwent partial reversal of contracture; in Group 2, contracture was reversed more completely, but the effect was transient. Hearts in Group 3 had contracture reversed completely to a level lower than prearrest end diastolic pressure. Hearts in contracture were profoundly depleted of high-energy phosphates (ATP, 9% of control; creatine phosphate, 27%) and the success of contracture reversal was parallelled by the extent to which each solution repleted ATP and PCr. Ventricular contracture produced by energy depletion is rapidly reversed by restoration of oxygen to the myocardium. Reducing extracellular calcium by acalcemic perfusion is ineffective as an isolated measure but is synergistic with reoxygenation and enhances contracture reversal.