Ischemia of the myocardium results in a loss of ultrastructure and function. Tension generation is diminished or abolished, electrolyte imbalance occurs, and the ATP-generating capacity of the mitochondria is reduced. An intracellular accumulation of Ca2+ appears to precipitate many of these changes, the intracellular accumulation of Ca2+ being caused, in turn, by a failure of the ATP-dependent mechanisms responsible for maintaining intracellular homeostasis with respect to Ca2+. This hypothesis has been tested by the use of hypothermia, pretreatment with verapamil and a reduced extracellular Ca2+ to modify the events precipitated by an ischemic episode.