We investigated morphologic activation of lymphocytes in blood in a standardized, infection-free rat model and compared lymphocyte activation during rejection of heart grafts and that of lung grafts with other parameters of rejection. For heart grafts the other parameters were histology and palpation, and for lung grafts they were histology, bronchoalveolar lavage, and chest roentgenography. During acute rejection of heart grafts, lymphocyte activation in blood increased when histology of the heart grafts showed already moderate-to-severe rejection with myocyte necrosis. Lymphocyte activation in blood detected acute heart rejection clearly later than histology but somewhat earlier than palpation. During acute rejection of lung grafts, lymphocyte activation in blood increased when histology of the lung grafts showed the (early) vascular phase of rejection, without apparent tissue damage. Lymphocyte activation in blood detected acute lung rejection only slightly later than histology, at approximately the same time as bronchoalveolar lavage and earlier than chest roentgenograms. Lymphocyte activation was higher during acute lung rejection than during acute heart rejection. During "chronic" rejection of long-surviving heart grafts and lung grafts, lymphocyte activation in blood did not increase consistently. The early and strong increase of morphologic activation of lymphocytes in blood during acute lung rejection may imply for clinical transplantation that monitoring of lymphocyte activation in blood is more useful for early detection of acute rejection after lung transplantation than after heart transplantation.