In four of the 37 patients operated on for a pheochromocytoma in the last 12 years at Duke Medical Center, the tumor was unsuspected. The first of the four patients had stable blood pressure and pulse during the operative and postoperative period. Although the second patient was thought to have a normal response to surgery, in retrospect her blood pressure showed significant variation. In contrast, the other two patients had wide variations in blood pressure and pulse during the operative and postoperative period. Electron microscopy of the tumor demonstrated numerous densecore neurosecretory granules suggestive of pheochromocytoma in all four patients. In three of the patients in which measurements could be made, there was a high concentration of norepinephrine (NE) in the tumors that was diagnostic of a pheochromocytoma. Although tissue from the fourth patient was not available for biochemical analysis, his urine and blood tests as well as his ultimate demise from the tumor confirmed that he had a malignant pheochromocytoma. Based on a negative chromaffin reaction-which might be anticipated in a NE-containing pheochromocytoma-one of the patients with the smooth operative course was incorrectly diagnosed as an adrenocortical adenoma. We conclude that although patients with unrecognized pheochromocytomas do not inevitably have wide swings in blood pressure during surgery, this cannot be predicted in a given patient. Thus one should carefully evaluate all patients with suspicious retroperitoneal or intraabdominal masses for possible pheochromocytomas prior to resection of the masses.