In a rat heart model of cardiopulmonary bypass and ischemic cardiac arrest the potential additive protective effects of hypothermia and chemical cardioplegia have been investigated. Isolated rat hearts were subjected to a 2 minute period of coronary infusion with a cardioplegic or a noncardioplegic solution immediately before and also at the midpoint of a 2 hour period of hypothermic (20 degrees C) ischemic cardiac arrest. In the hypothermia plus cardioplegia group postischemic aortic flow recovered to more than 50% of its preischemic control value, myocardial energy phosphate content returned to near preischemic control levels, and creatine kinase leakage was moderate. By contrast, in the hypothermia alone group (coronary infusion with non cardioplegic solution) the postischemic functional recovery was less than 30% of its preischemic control value, cellular high-energy phosphate content was considerably reduced, and creatine kinase leakage was more than twice that observed in the hypothermia plus cardioplegia group. In addition to illustrating the additive nature and powerful protective properties of hypothermia and cardioplegia these studies serve to illustrate the utility of the isolated rat heart model for the primary assessment of procedures designed to protect the myocardium during ischemic cardiac arrest. The results and conclusions derived from this study were quantitatively and qualitatively similar to those obtained in a parallel study in the dog.