The sympathetic innervation of the rabbit heart, as a function of age, was studied by measuring the cardiac concentration of catecholamines and observing the anatomic distribution of sympathetic nerves by die monoamine fluorescense technique. The cardiac concentration of norepinephrine in late gestation was quite low; the levels rose progressively after birth to reach adult levels by about three weeks of age. Similar small amounts of epinephrine were found in the hearts at all ages. Substantially less change in adrenal catecholamines accompanied advancing age. At all ages a close correlation was noted between the norepinephrine levels and the histochemical demonstration of sympathetic innervation. Intensely fluorescent, terminal varicosities were observed within large preterminal nerve trunks only in the youngest animals, suggesting that the sympathetic nerves move into, rather than form within, die heart. Chromaffin cells were observed in the hearts at all ages.ADDITIONAL KEY WORDS norepinephrine epinephrine adrenal chromaffin cells myocardial catecholamines• Although the adrenergic nervous system plays an important role in the control of cardiac contractility in the mature mammal, its significance in the perinatal period is not clear. Physiologic and pharmacologic studies undertaken to assess the maturation of the autonomic control of the circulation have been largely concerned with the ability of young animals to respond to various physiologic stimuli, such as hypoxemia and carotid sinus hypotension, or to the injection of catecholamines (1). A number of observations in rabbits of varying ages suggest that the circulaFrom the Cardiology Branch, National Heart Institute, Bethesda, Maryland, and the Department of Pharmacology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania.This investigation was supported in part by U. S. Public Health Service Research Grant 1R01NB0-6707. Dr. Jacobowitz was a recipient of a Research Career Program Award, 5-K 3-N B-13, 935-02, from the National Institutes of Health.Accepted for publication April 29, 1968. tion of the newborn is under no (2), a lesser (3), or a comparable (1) degree of neural control, as compared to the adult. The development of the separate factors constituting an integrated circulatory response-the afferent, central, and efferent components of a vascular reflex, the responsiveness of the peripheral vasculature, and the direct inotropic and chronotropic effects on the myocardium -have not yet been analyzed quantitatively. The objective of the present investigation was to define more clearly the development of sympathetic innervation of the rabbit heart. The cardiac concentration of norepinephrine in fetal, neonatal, and adult animals was employed as an index of the maturity of sympathetic innervation because the heart's stores of norepinephrine are localized almost exclusively in intraceilular storage sites within the terminations of the sympathetic nerves (4). In addition, the monamine fluorescence technique of Falck and O...