During the embryonic development of the myocardium both undifferentiated cells and cells containing muscle-specific proteins divide. As the heart grows and approaches maturity, its muscle cells progressively lose their mitotic activity; myocardial cell enlargement then becomes the principal process by which the heart as a whole enlarges. Mitotic figures in nuclei of heart muscle cells are frequent in the neonatal rat but become very rare at about the third month of postnatal life. Both in the developing and adult animal the work load is one of the determinants of cardiac size. The cytologic features of cardiac enlargement depend on the stage of development of the heart at the time when the stimulus to growth occurs. A work load imposed on embryonic or early neonatal hearts results in enlargement characterized by an increase in both the number and size of myocardial cells. The adult heart enlarges only by enlargement of its component muscle cells. Division of ventricular muscle cells in mammals is not activated after cardiac injury. The inability of ventricular myocardial cells to regenerate stands in sharp contrast to skeletal muscle, which is capable of considerable tissue repair, involving both regeneration of individual fibers and reconstitution of the whole muscle.