Gastric mucosal phospholipids, and in particular those of the surface layer, play an important part in mucosal barrier function. This study examined whether the phospholipid composition of the full thickness gastric mucosa is changed in peptic ulcer disease and gastritis. The phospholipid composition of gastric mucosa from endoscopic biopsy specimens in 28 subjects (eight healthy controls, 12 patients with duodenal ulcer, and eight with chronic atrophic gastritis) was studied. In addition, the phospholipid composition of gastric mucosa was compared with that of duodenal mucosa in 10 patients with duodenal ulcer. As expected phosphatidylcholine and phosphatidylethanolamine prevailed in all three groups. Lysolecithin was the smallest component in the duodenal ulcer and chronic atrophic gastritis groups. The phosphatidylethanolamine value was higher in duodenal ulcer and lower in chronic atrophic gastritis compared with the control group. In chronic atrophic gastritis there was an appreciable amount of phosphatidylglycerol that was not present in patients with duodenal ulcer or in the control group. There was no significant difference in phospholipid composition between antral and duodenal sites in duodenal ulcer patients. In conclusion, the phospholipid composition of gastric mucosa changes in human gastrointestinal diseases but its relation to cellular functions needs further study.