In this study we measured phospholipase A (PLA) and C (PLC) activity of media filtrates and French Press lysates of the gastritis-inducing bacteria Helicobacter pylori. We report here that both H. pylori lysates and filtrates contain PLA1, PLA2, and C enzymes, which readily hydrolyze a radiolabeled dipalmitoylphosphatidylcholine (DPPC) and phosphorylcholine substrates, respectively. The specific activity of both PLA and C enzymes were greatest in the 6.5-7.0 and 8.4-8.8 pH ranges, respectively. Colloidal bismuth subcitrate (CBS) induced a dose-dependent inhibition of PLA2 and C activity of both H. pylori lysates and filtrates. This inhibitory effect of CBS on PLA2 was antagonized in a dose-dependent fashion by the addition of CaCl2 to the incubation mixture, suggesting that calcium and bismuth may be competing for the same site on the enzyme. In contrast, the ability of bismuth salts to inhibit PLC activity of H. pylori lysates was not antagonized by CaCl2. Employing a biophysical assay system for surface wettability, it was determined that H. pylori lysates had the capacity to remove a synthetic phospholipid monolayer off a glass in a dose-dependent fashion. This ability of the bacterial lysates to catalyze the transformation of a hydrophobic surface to a wettable state was significantly attenuated in the presence of bismuth salts. Our experimental results are, therefore, consistent with the possibility that H. pylori colonization compromises the stomach's barrier to acid by eroding a phospholipid lining, possibly a monolayer, on the surface of the gastric mucus gel and that this process is blocked in response to bismuth therapy.