From 1978 to 1984, six patients (four men and two women) with functioning extrapancreatic gastrinomas were treated at the University of Michigan Medical Center. In all but one patient, who was known to have a liver metastasis, selective portal and peripheral venous sampling was performed to localize the site(s) of increased gastrin levels. Serum levels of carboxy (C) and amino (N) terminal gastrin moieties were measured before surgery with region-specific antisera and N/C ratios were calculated. All patients underwent operative exploration and successful resection of all gastrinomas present including a single large liver metastasis in one case. The C-terminal gastrin level was elevated in all cases and the N/C ratios were well below 1.0 (greater than 1 is consistent with malignancy and metastases) in all but the one patient with a liver metastasis. All patients have remained clinically free of tumor and have had normal basal and secretin-stimulated gastrin levels for as long as 5 years after operation. Three of the patients had undergone previous total gastrectomies and had done well apart from persistent hypergastrinemia before resection of the tumor. Two patients have not undergone any type of gastric operation. Appropriately selected patients with Zollinger-Ellison syndrome, particularly those with extrapancreatic primary lesions, may be candidates for a curative resection.