From 1971-1986, 24 patients were diagnosed as having Zollinger-Ellison syndrome (ZES) and 22 patients had laparotomy. Of this group, gross tumor was identified in 15 of 22 patients. Ten of 15 patients had resection of their gastrinomas with the specific aim of curing the disease. This group had responded favorably to either cimetidine or ranitidine before operation. Preoperative transhepatic portal venous sampling (PVS) with gastrin determinations was performed in six patients; three patients had this procedure twice. The tumor was correctly localized by PVS in five of six patients. In four of six patients, the tumor was easily found at surgery. In two of six patients (33%) PVS was vital to intraoperative decisions. Criteria for biochemical cure are normal periodic fasting gastrin and secretin infusion tests. Of the 10 patients who had resection for potential cure, two patients failed within 48 hours of surgery on the basis of an elevated fasting serum gastrin level in one patient and a positive secretin infusion test in the other patient. Eight patients were considered cured with follow-up from 6 months through 15 years. Of the eight cured patients, the tumors were located as follows: four were extraintestinal and extrapancreatic, four were in the duodenal wall, one patient had a tumor located in the uncinate process of the pancreas, and one tumor was located in a lymph node along the lesser curve of the stomach. Two patients had mobilization of the pancreas and duodenum for a "blind" pancreatoduodenectomy based on preoperative PVS (2 procedures each patient). In one patient a 3-mm gastrinoma was enucleated from the posterior uncinate process. The second patient had pancreatoduodenectomy with findings of two duodenal wall gastrinomas. Both patients remained cured of ZES beyond 2 years. It is concluded that PVS does indeed locate some tumors before operation, even those not easily found at surgery. ZES can be cured by an aggressive approach combining preoperative tumor localization and tumor resection. Of the eight patients biochemically and perhaps biologically cured, follow-up was greater than four years in five patients, greater than two years in two patients, and beyond six months in one patient.