With the advent of cyclosporin therapy, cardiac transplantation has become an effective procedure in treating selected patients with end-stage myocardial diseases. Because cyclosporin masks the clinical symptoms of rejection, the endomyocardial biopsy has become the "gold standard" for grading allograft rejection. Many classification systems for grading rejection have been proposed, largely based on the original work of Billingham. Comparisons among these schemes, useful for the evaluation of results from different centers, might be facilitated by adoption of the concept of stable versus unstable acute rejection. Many questions remain regarding the mechanism of acute rejection, the diagnosis of chronic rejection by endomyocardial biopsy, the effects of therapy, and the pathogenesis of endocardial lymphocytic infiltrates, to name a few. However, the recently developed techniques of in situ hybridization and propagation of lymphocytes from endomyocardial biopsies in conjunction with immunohistochemistry and electron microscopy may bring us to a new level of sophistication in understanding the pathology of cardiac transplantation.