Background-Gastric mucosal surface hydrophobicity (GMSH) is an essential component of the mucosal defence system that is decreased by Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs). Gastric ulcers occur predominantly in elderly subjects, and may thus reflect diminished mucosal resistance. Aims-To investigate whether aging decreases GMSH. Patients-One hundred and twenty patients without peptic ulcer disease were divided into three age groups: I (41 years or below); II (41-64 years); and III (65 years or above). Methods-Biopsy specimens were taken from the antrum, corpus, and cardia for histology (Sydney system), urease testing for ii pylori, and for contact angle measurement of GMSH with a goniometer. The presence of specific H pylori antibodies was checked by immunoblotting. Results-Fifty two patients (:43%) were infected, and 68 were uninfected with Il pylori. GMSH at all biopsy sites was lower in H pylori infected subjects (p=0.0001), but also decreased with age independently of infection status (p=0.0001). The most notable decrease in GMSH occurred between age groups I and II in those with, and between age groups II and III in those without, H pylori infection. GMSH was greater in antral than in corpus mucosa in both infected (p=0.0001.) and uninfected patients (p=0.0003). Conclusions-A physiological decrease in GMSH with aging may contribute to the risk of ulcer development in the elderly, and may act synergistically with H pylori and/or NSAIDs on gastric mucosal defence.