To measure their relative upper gastrointestinal irritant potential, either 5 mg amiloride and 50 mg hydrochlorothiazide (twice daily) or 24 mEq wax-matrix potassium chloride (three times a day) were given to 30 normal subjects with no prior endoscopic abnormalities in the esophagus, stomach, or duodenum. All subjects received glycopyrrolate, 2 mg (3 times a day) to slow gastric emptying. Repeat endoscopy after 7 days of treatment with wax-matrix potassium chloride revealed that 10 of 15 (67%) of the subjects developed one or more gradable upper gastrointestinal lesions (esophageal ulcer, gastric ulcer, eight cases of one or more mucosal erosions, and four cases of hyperemia or edema of the esophagus, stomach, or duodenum). Four subjects (27%) taking amiloride/hydrochlorothiazide developed either mild hyperemia or edema, but there were no erosions or ulcers in this group.