Routine enzymatic and electrocardiographic diagnosis of postoperative acute myocardial infarction (AMI) is frequently inconclusive. The detection and quantitation of isoenzymes of lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), especially the cardiac-specific CPK-MB isoenzyme, have allowed earlier recognition of AMI in nonsurgical patients. Serial monitoring with these methods has been utilized during the postoperative period in 20 noncardiac surgical patients and 100 patients undergoing coronary artery bypass grafting (CABG). In the noncardiac surgery group, both isoenzymes were accurate in diagnosing AMI in the early postoperative period. Of the 100 patients in the CABG group, CPK-MB appearance in 21 correlated with AMI by electrocardiogram. The absence of CPK-MB postoperatively in 49 patients permitted a 73% incidence of new ECG abnormalities to be effectively resolved. Autopsy confirmation of AMI was obtained in two patients with nondiagnostic ECG, but with elevated CPK-MB. The elevated CPK-MB without ECG evidence of AMI in the remaining patients could possibly be explained by varying degrees of myocardial damage produced by intraoperative cardiac manipulation. These data demonstrate the value and sensitivity of CPK-MB isoenzyme determinations in the early recognition of postoperative acute myocardial infarction.