Administration of NGF to newborn and adult rats elicits a selective increase in TH and DBH both in sympathetic ganglia and adrenal medulla. This effect does not depend on intact preganglionic cholinergic fibers. The augmented enzyme activity results from enhanced enzyme synthesis since it can be abolished by cycloheximide and NGF has been shown to enhance the incorporation of [3H]leucine into DBH molecules. The responsiveness of the adrenal medulla to NGF is also supported by light and electron microscopic autoradiograms which show that intravenously injected 125I-NGF is accumulated with high selectivity in adrenal chromaffin as compared to adjacent adrenal cortical cells. In spite of the many similarities between the response of the adrenergic neurons and adrenal chromaffin cells to NGF, there are also two distinct differences. (a) In newborn rats the ratio between the TH increase effected by a single and 10 subsequent daily injections of NGF is 1:2 in the adrenal medulla and 1:7 in the superior cervical ganglia. (b) If adrenal medullae are transferred to organ culture after intravenous injection of NGF, maximal TH response is initiated 60-90 min after NGF administration. In superior cervical ganglia only a half-maximal response is initiated at that time. After a stationary phase a second increase starts after about 6 h to reach the maximum after 12 h. The biphasic time course of the initiation of TH induction by NGF in sympathetic ganglia is in agreement with the time course of 125I-NGF accumulation after intravenous injection27 reflecting the moiety of NGF reaching the cell bodies of the adrenergic neurons directly by the blood stream (initial accumulation) and by retrograde axonal transport (second phase).