Induction of ischemia in the open-chest dog or isolated rat heart caused a series of critical changes in carnitine-related metabolism. As a result of these metabolic changes, the LCACA/carnitine ratio rapidly increased which, in turn, may have reduced the activity of mitochondrial ANT and a number of other enzyme systems necessary for normal heart function. Carnitine administration apparently reversed these carnitine-linked metabolic changes and protected the ischemic myocardium. Possible mechanisms for the protective action of carnitine were discussed.