Myocyte injury in acute cardiac transplant rejection was studied ultrastructurally in 45 patients. Mild myocyte injury consisted of increased glycogen granules and mitochondria, and condensation and streaming of myofilaments. More severe cell injury was characterized by clumping of Z-band material at the periphery of the cell and loss of sarcomeric units. Cell swelling was not seen, and intramitochondrial dense deposits (indicative of irreversible cell injury) were rarely seen. Restoration of normal myocyte ultrastructure occurred after treatment for rejection. Although the light microscopic appearance of moderate or severe acute rejection may suggest myocyte necrosis, this is rarely observed ultrastructurally. We conclude that the majority of cell injury in acute rejection is potentially reversible.