Ionic permeability of the gastric mucosa was measured in six patients with an acute exacerbation of severe generalized rheumatoid arthritis receiving either aspirin and prednisone or aspirin and indomethacin as therapy. The results were compared with those in four patients with benign gastric ulcer and nine normal subjects. Compared with controls H(+) concentration was decreased and Na(+) concentration increased while corrected H(+) flux out of the lumen and Na(+) flux into the lumen were significantly increased in the patient groups, indicating increased mucosal permeability. Abnormality of the gastric mucosal barrier persisted in two patients despite healing of their ulcers. Mucosal permeability of patients with rheumatoid arthritis and gastric ulcer did not differ significantly from one another. One rheumatoid patient with a gastric ulcer showed no difference in mucosal permeability to that of the other rheumatoid patients. These studies suggest that increased H(+) ion loss contributes to the apparent hyposecretion of acid in patients gastric ulcer; persistence of an abnormal gastric mucosal barrier to H(+) ions may explain the high recurrence rate of gastric ulcers; and an abnormal gastric mucosal barrier may be a precursor to gastric ulceration in rheumatoid arthritis.