Endomyocardial biopsy is currently the best method to monitor cardiac allograft rejection. The histologic criteria of infiltration by mononuclear cells with pyroninophilic cytoplasm and acute myocyte necrosis indicate immunologic activation and require an increase of immunosuppressive therapy. Of particular concern is the persistence of necrotic fibers on biopsies for some time after ischemic episodes associated with the transplant procedure and after acute rejection episodes. Because the presence of acute myocyte necrosis plays a key role in the clinical decision on immunotherapy, we evaluated the resolution pattern of acute necrotic fibers under standard immunosuppression treatment. Myocardial infarction of the posterior papillary muscle was surgically induced in two groups of dogs that were killed (three from each group) at 4, 7, 14, and 21 days after surgery. The first group consisted of 12 control animals, and the second group was composed of 12 dogs, immunosuppressed with cyclosporine, methylprednisolone, and prednisone. The histologic sections demonstrated a persistence of myocyte necrosis for 14 days after infarction in the treated group but for only 7 days in the untreated control group. This slow resolution pattern needs more emphasis in clinical practice. Criteria other than myocyte necrosis should be used to differentiate ongoing from resolving rejection after the first rejection episode. Preservation injury may persist for 2 weeks after transplantation and be misinterpreted as acute rejection.