In a 37-year-old patient with Ménétrier's disease, 51Cr-albumin and alpha 1-antitrypsin (alpha 1-AT) output was measured simultaneously in gastric juice and feces. While the 51Cr-albumin studies demonstrated a threefold increase in gastrointestinal protein loss, alpha 1-AT was found in normal quantities in gastric juice and feces. The histamine H2 antagonist, ranitidine, led to a marked reduction in gastric protein loss, as evidenced by decreased 51Cr activity in the stomach. Studies of protein loss in the gastric juice during pentagastrin stimulation (6 micrograms/kg/h) showed that the 51Cr-albumin output paralleled the volume secreted, whereas alpha 1-AT decreased with lower pH values, not being detectable below pH 3. This probably results from peptic degradation of alpha 1-AT at low pH. We conclude that fecal alpha 1-AT determination cannot be used for the assessment of protein-losing gastropathy in patients who are not achlorhydric.