Half of all patients with the Zollinger-Ellison syndrome treated by total gastrectomy will eventually die from their tumor. The clinical course of four patients observed for at least four years is discussed. Three patients had liver metastases, responsible for the death of two and seriously affecting the third. The fourth had extensive tumor around the pancreas plus mesenteric metastases that were removed. The patient is doing well. Hepatic artery ligation, streptozotocin therapy, and internal radiation of the tumor were tried in an attempt to control the hepatic metastases. Hepatic scans, the serum gastrin response to calcium infusion, and hepatic angiography are useful techniques to assess continued tumor growth following total gastrectomy.