The problem of hypergastrinemia in patients with the syndrome of multiple endocrine neoplasia (MEN type 1) has become increasingly controversial since the introduction of the antisecretory H2 antagonists for the treatment of the Zollinger-Ellison syndrome (ZES). One of the questions in the management of ZES is whether the malignant potential of the gastrinomas or the recurrent complications of ulcer will be the ultimate cause of death. Another problem is whether the association of MEN is a favorable or unfavorable factor to the prognosis of patients with ZES. Hypercalcemia contributes to excessive gastrin secretion, thereby casting doubt on the diagnosis of ZES in the presence of MEN. Patients with MEN are also more likely than patients with ZES not to have gastrinoma on an exploratory laparotomy. The existing controversy concerns the choices of therapy in instances of progressive ZES associated with MEN or when there is a failure to detect a primary gastrinoma when exploration is performed. To highlight the debate, the clinical courses of two patients, observed during two and three decades, respectively, are presented. These patients were receiving high doses of cimetidine; in addition, conventional surgical treatment for ulcer and repeated biopsies for gastrinoma were performed. After total gastrectomies (as life saving procedures), both patients are well.