The present study was undertaken in order to assess the effects of an acute and purely extracellular depletion of Mg during subtotal global ischemia and/or during post-ischemic reperfusion in the isolated rat heart. Mg depletion during reperfusion only or during ischemia plus reperfusion induced a significant reduction in post-ischemic recovery of cardiac function. Mg depletion during ischemia alone induced only a minor reduction in inotropy and coronary flow. Myocardial ATP at the end of the experiment was lowered in the groups of hearts deprived of Mg during ischemia plus reperfusion or during reperfusion only. A secondary finding was the demonstration of positive chronotropic and negative inotropic effects of the removal of extracellular Mg in non-ischemic hearts. It is concluded that, in a minor to moderate ischemic injury as in the present study, acute removal of extracellular Mg may lead to impairment of post-ischemic cardiac function and metabolism.