In the case that long term treatment with cimetidine could lead to a reduction of the parietal cell mass, there would result important therapeutic consequences. To investigate this possibility, 26 patients with duodenal ulcer were prospectively studied while on treatment with 1 g daily of cimetidine for two six-month periods separated by a two-week interruption of the therapy. No significant changes in pentagastrin-stimulated gastric acid secretion were observed after seven to 14 days off cimetidine, following six and twelve months of treatment. Cimetidine therapy had a significant effect on ulcer pain and antacid consumption. There were reductions of 11% and 10% from the initial figures in the proportion of ulcer niches seen endoscopically, after six in twelve months of treatment respectively. Some patients without a visible duodenal niche on initial endoscopy showed one at subsequent examinations. The sudden interruption of cimetidine treatment after six months was followed by the development of a gastric ulcer, previously absent, in three patients, one of whom had an upper gastrointestinal haemorrhage. There were no extragastric complications in spite of the doses and the duration of treatment. The authors consider that maintaining patients on one gram per day of cimetidine for one year is useless.