A model of heterotopic cardiac transplantation for diagnosis of rejection is described. Heterotopic cardiac transplantations were performed in the thorax using the left innominate artery as an arterial supply with venous return into the superior vena cava. Six pairs of mongrel dogs underwent cardiac transplantation using this technique. Two dogs died postoperatively on the 2nd and 3rd day due to respiratory failure. Another four donor hearts arrested their beats in 6 to 8 postoperative days (mean 6.3 days) resulting from acute cardiac rejection. Serial echocardiographic recordings were found to be a reliable measure of acute cardiac rejection, since the left ventricular wall thickness of the donor heart increased until the donor heart stopped by rejection. Endomyocardial biopsy was easy to perform by passage of flexible cardiac biotome into the right ventricle of the donor and the recipient heart through the right internal jugular vein. Pathological findings revealed that early changes of the donor heart were interstitial edema caused by myocardial ischemia. This was followed by lymphocyte infiltration around peripheral coronary arteries and acute rejection resulting in myocyte necrosis.