Although the mechanism of gastric mucosal protection is multicomponential, the initial brunt of luminal insult falls on the layer of mucus weakening its physicochemical characteristics and is intimately associated with gastric disease. Hence, the agents capable of strengthening the qualities of mucus gel, associated with its protective function, are becoming increasingly popular in peptic ulcer therapy. Evaluation of the efficacy of these types of drugs requires delineation of their direct effect on the mucus layer constituents, from those evoked in the chemical composition of mucus as a result of prolonged drug administration. Studies with mucus layer strengthening agents indicate that such drugs as sucralfate and De-Nol interact tenaciously with the mucus gel and in essence seal the underlying mucosal surface from the noxious luminal contents. These drugs and other new antiulcer agents like sofalcone, geranylgeranylacetone and stable prostaglandin analogs are also capable of enhancing mucus gel viscosity and its hydrogen ion impedance ability. Furthermore, the majority of these drugs exert an inhibitory effect on peptic degradation of gastric mucus, and the colloidal bismuth preparation (De-Nol) is also capable of prolongation of the luminal availability of epidermal growth factor. The data on gastric mucus gel, following prolonged administration, show that these drugs enhance the lipid content of the mucus gel, and increase both the mucus coat dimension and the proportion of the high molecular weight form of its mucin component. These changes result in the improvement of viscoelastic, permselective and hydrophobic properties of gastric mucus. Hence, continuity of the function of mucus layer perimeter of mucosal defense is maintained.