Six patients with severe medical disorders and profound hypothermia are presented who had elevated total serum creatine phosphokinase (CPK) and CPK-MB isoenzyme activity without clinical or postmortem evidence of acute myocardial infarction. Experiments in dogs indicate that hypothermia reduces total CPK activity in both striated and myocardial muscle resulting in increased serum enzyme activity. These data suggest that profound hypothermia may result in diffuse striated and cardiac muscle cellular injury without evidence of discrete infarction with consequent release of CPK-MB isoenzyme into serum.