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Lymphocytic accumulation in different areas of the myocardium during different phases of acute rejection were studied in rat heterotopic cardiac and cardiopulmonary allograft and isograft transplantation models. Indium 111-labeled syngeneic lymphocytes were injected 1 to 7 days after transplantation, and accumulation of the labeled cells in the graft was determined 24 hours later. The cardiac graft was divided into three segments: right ventricular (RV) free wall, epicardial portion of the left ventricle (LV) plus RV septum, and endocardial portion of the LV. In the subsequent heart-lung transplantation group, the LV epicardial portion plus RV septum segment was subdivided into LV epicardial portion and RV septum. Lymphocytic accumulation in each segment was compared between three groups according to the day the animal was killed after transplantation: days 2, 3 (group 1), days 4, 5 (group 2), and days 6, 7, 8 (group 3). Lymphocytic accumulation caused by rejection in group 1 and group 2 of both the cardiac and cardiopulmonary allografts showed significantly different intramyocardial distribution (p less than 0.01). Lymphocytic accumulation was consistently highest in RV free wall and lowest in LV endocardial portion. In group 3 specimens, lymphocytic accumulation was symmetrical in both the cardiac and cardiopulmonary allografts. In the cardiac allograft, the lymphocytic accumulation increased sharply on day 4 then declined to a nadir. This transient increase was not so pronounced in the cardiopulmonary allografts. The significantly decreased intramyocardial lymphocytic accumulation in group 2 of the cardiopulmonary allografts when compared with the cardiac allografts (p less than 0.01) is compatible with the clinical observation of a lower incidence of acute heart rejection in heart-lung transplant recipients. These data show an asymmetric accumulation of lymphocytes during acute heart rejection, which is due to increased lymphocytic affinity for the RV free wall.