The ouabainlike factor (OLF) is thought to be an important modulator of salt and water metabolism. Plasma OLF could be derived from the central nervous system and/or the adrenal gland. Since the adrenal medulla is of neural origin, the cytology of pheochromocytoma of adrenomedullary origin resembles that of neuronal cells. Ouabainlike immunoreactivity (OLI) is, in fact, present in the adrenal medulla as shown by immunohistochemistry. The plasma levels of catecholamines and OLI were significantly elevated during surgical extirpation of pheochromocytoma in this case. To clarify the origin of circulating OLI in a patient with pheochromocytoma, the relationship between plasma OLI and catecholamines during adrenalectomy was investigated. Plasma catecholamine levels exceeded the normal reference interval, and plasma OLI was positively correlated with the patient's plasma level of norepinephrine. The peak level during operation was about 10 times higher than the baseline level. Both levels reached a maximum when the tumor was mechanically pressed, and then gradually decreased thereafter. The level of OLI in the tumor was higher than that of the normal adrenal cortex. When OLI in the tumor was characterized by reversed-phase high-performance liquid chromatography, the retention time of OLI corresponded with that of authentic ouabain. These results suggest that the circulating OLI in this patients was derived mainly from the pheochromocytoma of adrenomedullary origin.