Acid and pepsin have been designated the "aggressive factors" in peptic ulcer because they are essential for ulcer formation and because a reduction in their luminal concentrations is usually followed by ulcer healing. Acid enables peptic aggression by converting pepsinogen to pepsin, by providing the highly acidic pH required for pepsin activity, and by denaturing proteins, thereby increasing their susceptibility to the action of pepsin. Pepsin causes peptic aggression by hydrolyzing peptide linkages which bind together the constituent amino acids of proteins. The first step in this reaction is the formation of a complex between the active site of pepsin and the protein substrate. Sucralfate, which is the basic aluminum salt of sucrose octasulfate, inhibits this step by forming an electrostatic complex with proteins. As such, sucralfate inhibits peptic aggression without decreasing acid-pepsinogen secretion or raising intragastric pH. Because of its affinity for proteins and its insolubility and inherent viscosity in acid, sucralfate forms a physical coating over the ulcer crater. This coating further inhibits peptic aggression by producing a barrier to the diffusion of acid and pepsin. Additionally, the basic aluminum moieties of sucralfate may serve to buffer hydrogen ions as they attempt to permeate the viscous layer. The sum of these effects appears to explain the ability of sucralfate to accelerate the rate of healing of peptic ulcer.