H2-histamine receptor blocking agents, metiamide and cimetidine, were assessed in 7 patients with Zollinger-Ellison syndrome (serum gastrin > 300 .mu.g/ml, basal acid output > 15 meq/h, ratio of basal acid output to maximal acid output > 0.5). I.v. or oral administration of the drugs lowered acid secretion by at least 70% in all cases. Subsequent treatment of 6 patients for 3-15 mo. (oral therapy) and 1 patient for 1 mo. (i.v. therapy) showed that the drugs abolished symptoms in all 7, abolished diarrhea in 5, allowed ulcer healing in 6 and and were well tolerated without adverse effects in 7. No patient failed to respond to the drug, although 1 died from tumor progression and 2 required total gastrectomy for complex reasons. Patients with Zollinger-Ellison syndrome apparently can be managed medically and, in light of current mortality trends, gain little from the extra risks attending total gastrectomy.