Background & Aims: Gastric mucosal hydrophobicity is reduced in Helicobacter pylori infection. Infection density is increased in duodenal ulcer (DU) compared with H. pylori gastritis alone, but it is unknown whether there is a corresponding difference in hydrophobicity or whether hydrophobicity is related to infection density or to mucus lipids. The aim of this study was to determine the relationship between H. pylori infection density and mucosal hydrophobicity, and between mucus lipids and hydrophobicity, and to compare results in patients with H. pylori-induced gastritis with and without DU, Methods: Fifty-four patients, including 29 H. pylori-positive (15 with DU and 14 with gastritis alone) and 25 H. pylori-negative controls, were studied. Hydrophobicity was determined by goniometry and infection density by histology. Mucus lipids were determined by colorimetry and phospholipase A(2) activity by radioenzymatic assay, Results: Hydrophobicity was reduced in DU compared with gastritis alone (39 degrees vs. 48 degrees; P < 0.05) and with healthy controls (39 degrees vs. 60 degrees; P < 0.0001). Hydrophobicity correlated with infection density (Rs = -0.55; P < 0.01), Mucus triglyceride level was modestly increased with infection, but mucus phospholipids or lipolysis were unrelated to H. pylori and hydrophobicity, Conclusions: Mucosal hydrophobicity is reduced in H. pylori-positive patients with DU compared with those having gastritis only. Hydrophobicity correlates with infection density but not with mucus lipid levels.