Endomyocardial biopsy (EMB) is widely used, but the effects on the endocardium have not been studied in detail. If repetitive biopsies are performed, as in the monitoring of cardiac transplants, there is a chance of sampling a previous EMB site. This study investigates changes in EMB site morphology over a period of 0 to 30 days in a primate model. Organization of thrombus, necrosis of myocytes adjacent to the biopsy site, and the presence of mononuclear cells (including T lymphocytes) surrounding the biopsy site indicated a potential for confusion with the appearances associated with acute or resolving cardiac rejection. We have encountered this problem in clinical practice. Knowledge of EMB site morphology aids in the interpretation of EMB specimens.