Chromaffin cells in the adrenal medulla are specialized for the synthesis, storage, and secretion of catecholamines. These cells are innervated by preganglionic sympathetic neurons in the splanchnic nerves, and, because of their unique blood supply, are exposed to unusually high concentrations of glucocorticoids in the venous drainage from the adrenal cortex. Splanchnic nerve stimulation appears to be the most important determinant of adrenomedullary function. Chromaffin cells synthesize catecholamines from tyrosine. Splanchnic nerve stimulation leads to an increase in the activity of several of the catecholamine biosynthetic enzymes, and to an increase in the rate of catecholamine biosynthesis. Glucocorticoids cause the induction of the enzyme noradrenaline N-methyltransferase, and so are particularly important for the synthesis of epinephrine. Catecholamines are stored, together with ATP, Ca2+, and protein, in secretory vesicles known as chromaffin granules. Splanchnic nerve stimulation is the physiological stimulus for catecholamine secretion. Stimulation of the splanchnic nerves results in the release of ACh from nerve endings in the adrenal medulla. ACh causes an increase in the permeability of the chromaffin cells to Ca2+, and thereby leads to the entry of Ca2+ into the cells. Ca2+ then causes the secretion of catecholamines and of other chromaffin granule constituents from the chromaffin cells by exocytosis. The biochemical mechanisms of exocytosis, and the mechanism by which Ca2+ stimulates this process, are still unknown.