From August 1984 to March 1989, 1535 endomyocardial biopsy specimens from 79 heart transplant patients were evaluated for rejection. Electron microscopy was performed on 664 of these specimens. Three hundred eighty-eight were diagnosed as accelerating, moderate, severe, or resolving acute rejection. Regeneration of adult human myocardium after acute rejection was seen in 22 specimens. Regeneration was identified in myocytes showing ultrastructural and light microscopic evidence of nuclear division and cytoplasmic dedifferentiation. Regenerating cell nuclei showed complex surface involution and large nucleoli. Cytoplasm appeared embryonic with abundant ribosomes, rough endoplasmic reticulum, and numerous mitochondria. Sarcomerogenesis was associated with cytoplasmic and subsarcolemmal clumps of Z band material. Myofibrillogenesis occurred throughout the cytoplasm but was favored in subsarcolemmal areas. Intercalated discs were primitive and depended on the differentiation state of adjoining myocytes. Nexus junctions were not seen. We conclude that myocyte injury during acute rejection of heart transplants is reversible and that adult human myocytes have a hitherto unsuspected capacity for regeneration.