Immunoreactive oxytocin and arginine vasopressin (AVP) were measured in the adrenal medulla of both rat and man as well as in tissue from two pheochromocytomas using highly specific RIAs. In all instances, oxytocin predominated over AVP. The concentrations of oxytocin ranged from 19.9-162.7 pg/g tissue, whereas those for AVP were 9.8-102 pg/g. These values are far greater than those found in plasma. The oxytocin- and AVP-related neurophysins were also present in large quantities in human adrenal medulla and pheochromocytoma. Identity of the peptides was confirmed by demonstrating parallel immunoreactivity with standard compounds and by the high performance liquid chromatographic profiles. In experiments carried out in rats, the source of the adrenal medullary AVP and oxytocin did not appear to be the paraventricular nucleus. It is postulated that the neurohypophysial peptides may have a regulatory function in the secretion of catecholamines.