SUMMARYAlthough in most patients with duodenal ulcer disease the ulcer heals after 8 weeks of treatment with standard doses of H2blockers or other agents, in about 10% the ulcer does not heal. These patients are considered ‘refractory’to treatment. Reasons often cited for non‐healing include poor patient compliance, cigarette smoking, and non‐steroidal anti‐inflammatory drug (NSAID) use. Gastric acid hypersecretion also appears to be an important factor in non‐healing with standard doses of antisecretory agents. We have defined idiopathic gastric acid hypersecretion as a basal acid output of>10 mmol/h in the absence of an elevated fasting serum gastrin level (or a negative secretin test if gastrin level>100 pg/ml) to exclude persons with Zollinger‐Ellison syndrome. Among the acid/peptic‐related disorders in which idiopathic gastric acid hypersecretion should be considered are refractory duodenal ulcer, refractory gastro‐oesophageal reflux disease (especially patients with oesophagitis), postbleeding duodenal ulcer, and certain rare disorders such as hereditary angioedema. Some children with atypical abdominal pain may also be hypersecretors of gastric acid.Once identified, patients with refractory duodenal ulcer or gastrooesophageal reflux disease are treated with incremental doses of ranitidine titrated against the level of gastric acid secretion that remains during therapy. Ranitidine was selected to avoid the dose‐related antiandrogenic effects and potential hepatic cytochrome P450 system‐related drug interactions that may occur with cimetidine. In most cases of refractory duodenal ulcer, doubling the standard dose of ranitidine (to 300 mg b.d.) is sufficient to achieve symptomatic relief and mucosal healing. Higher doses appear to be necessary for refractory oesophagitis. To date, no side effects have been associated with high doses of ranitidine (up to 1800 mg/day) for periods of longer than 6 months. Idiopathic gastric acid hypersecretion is an important factor in explaining why not all patients respond to a ‘standard’ulcer‐healing dose of H2blocker, and it provides a rationale for use of higher‐dose therapy as a safe and effective alternative to omeprazole or to combination drug therapy in r