A novel explanation for the action of sucralfate in gastric ulcers has been proposed based on a new theory for gastric mucosal protection derived, in effect, from the very common industrial practice of adsorbing surfactants to surfaces needing protection against acid. Standard physical tests have been employed to show that sucralfate is highly surface-active at both liquid and solid interfaces, with the capability to be adsorbed-but not as active as the indigenous surface-active phospholipid (SAPL). This finding can explain the ability of sucralfate to "bind" to an ulcer site. Unlike SAPL or surfactants in general, adsorbed sucralfate does not render hydrophilic surfaces hydrophobic, suggesting a dual role in substituting for both SAPL and the mucus needed to stabilize it. Electron microscopy, using a novel fixation procedure specifically designed to allow for the known properties of any gastric mucosal barrier, revealed essentially the same oligolamellar lining of SAPL as previously reported in rats. Prolonged (16-day) exposure to sucralfate did not appear to change the situation, whereas there were as many, if not more, lamellar bodies (freshly secreted SAPL) adjacent to the stomach wall. Mucus-free oxyntic ducts showed the same oligolamellar lining as controls. An interesting new finding was the presence of oligolamellar SAPL as the intergranular matrix of gastric mucus-as though preparing to protect the next layer in anticipation of the surface mucin granules being eroded.