Histological examination of the myocardium by endomyocardial biopsy is a standard method of monitoring the presence of acute rejection in the transplanted heart. The histopathological consequences of the biopsy procedure itself have been investigated in non-transplanted hearts in the baboon. Organization of thrombus, necrosis of myocytes adjacent to the biopsy site, and mononuclear cells (including T lymphocytes) surrounding the biopsy site appear after biopsy; should a subsequent biopsy be taken from this area, these appearances may be confused with the appearances associated with acute or resolving cardiac rejection. This problem has been encountered in the clinical transplant programme. Observations on the myocardial histopathological changes resulting from brain death and from parasitic infestation, both of which may also lead to confusion in the interpretation of endomyocardial biopsies, are also presented. Awareness of these factors in patients with heart transplants should lead to caution in the interpretation of the histopathological features and may avoid unnecessary extra immunosuppression early after transplantation. Observations indicate that endomyocardial biopsy should not be the sole method of monitoring for the development of acute rejection.