The purpose of this study was to prospectively determine what effect total joint arthroplasty had on the myocardial-associated isoenzymes of serum creatine kinase (CK-MB) and lactate dehydrogenase (LD-1:LD-2). Fifty patients treated with total joint arthroplasty of the hip or knee had isoenzyme determinations using automated spectrophotometry and agarose gel electrophoresis. Skeletal muscle injury associated with the trauma of surgery resulted in significant elevations of the absolute value of CK-MB; however, the percentage of CK-MB comprising total CK activity and LD-1:LD-2 did not rise significantly in patients who did not experience postoperative myocardial infarction. It is important to determine both serum CK-MB and LD-1:LD-2 in suspected postoperative myocardial infarction since false positive elevations of CK-MB can occur. Elevations of CK-MB exceeding 50 International Units/liter or 5% of the total CK activity combined with LD-1:LD-2 exceeding 1.0 should not be attributed to skeletal muscle injury alone following total joint arthroplasty of the hip or knee.