The present investigation attempts to correlate the appearance of catecholamines to receptor-induced metabolic events (adenyl cyclase-phospho-diesterase) in the developing human heart. Adrenergic innervation, examined with the Falck-Hillarp fluorescence technique as well as by electron microscopy, reveals the presence of catecholamine-containing cells in or near the fetal heart at all ages studied (8–18 weeks). In most instances these cells occur either in association with extrinsic nerves along the aorta and pulmonary trunk or in the interatrial septum. Ultrastructural features of these cells include dense core vesicles. Acetylcholinesterase positive cardiac nerves and ganglion cells are observed. Highest basal activities of adenyl cyclase are found at the sixth fetal week. The enzyme is activated by fluoride ion from the eighth through the seventeenth fetal week, but not by catecholamines. Glucagon stimulates this enzyme at the seventeenth fetal week. Phosphodiesterase activity is progressively increased from the eighth to the seventeenth weeks and is inhibited by aminophylline from the tenth through the fifteenth week. Although catecholamine cells are present in the fetal heart, adrenergic fibers are absent at all ages studied. Failure to observe adrenergic fibers may correlate with the lack of hormonal activation of receptor mechanisms.