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We report representative serum enzyme changes after cardiac transplantation in 20 patients receiving post-transplant therapy with cyclosporine. In general, the changes resembled those after acute myocardial infarction or coronary artery bypass surgery, but were more prolonged. Cardiac biopsy or episodes of cardiac rejection did not usually alter serum enzyme activities. Cyclosporine A toxicity appeared to be responsible for increases in serum transaminases (alanine and aspartate) and lactate dehydrogenase-5 activities. Serum gamma-glutamyltransferase activities were intermittently, and inexplicably, increased for months after the transplant.