A novel hypotensive peptide was discovered in human pheochromocytoma by monitoring the elevating activity of platelet cAMP. Since this peptide is abundant in normal adrenal medulla as well as in pheochromocytoma tissue arising from adrenal medulla, it was designated "adrenomedullin". The peptide, consisting of 52 amino acids, has one intramolecular disulfide bond and shows slight homology with calcitonin gene related peptide. It was found to elicit a potent and long lasting hypotensive effect. The peptide circulates in blood in a consider able concentration, but it was not found in brain. These data suggest that adrenomedullin is a new hormone participating in blood pressure control. Occurrence of adrenomedullin indicates the possible existence of a novel system for circulation control. (C) 1993 Academic Press. Inc.