The process of chronic rejection is the limiting factor in long term survival after cardiac transplantation. As part of a study of this process in experimental orthotopic heart transplantation, morphological changes during the course of rejection are described in DLA-identical beagle littermates, obtained by serial percutaneous cardiac biopsy. A total of 153 biopsies were performed on 19 dogs. Mean survival time was 88.11 days (14--494 days) without the use of immunosuppressive therapy. Eight dogs, surviving only 4 weeks, showed a histological pattern that resembled delayed acute rejection, with extensive lymphocellular infiltrate, vascular damage, and myocytolysis. In the 11 dogs which survived more than 4 weeks there was a slight and sometimes transient lymphocellular infiltrate. But progressive vascular lesions could be seen from the 2nd week consisting mainly of medical proliferation involving intramural vessels as well as epicardial vessels. Capillary changes were prominant and the rate of capillary damage seems to be an indication of graft survival prognosis.