Continuous treatment of three Zollinger-Ellison patients with histamine H2-receptor antagonists for 14, 26 and 31 months resulted in effective relief of complaints and marked reduction in gastric acid secretion. In one of the patients the dose of cimetidine had to be doubled after 15 months of treatment because of a rise in basal gastric acid secretion accompanied by recurrent diarrhea. Fasting and secretin-stimulated serum gastrin levels were not affected by long-term treatment with histamine H2-receptor antagonists. No side-effects were observed in the three patients on long-term treatment.