Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]ethyl ] amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) is a novel H2-receptor antagonist that also exhibits a potent gastroprotective action against ethanol damage. This study was designed to ascertain under physiological conditions the effect of ebrotidine on the secretion of gastric mucus, probably the main component of the mucosal barrier. Two groups of 20 rats each were given a daily oral dose of 10 or 35 mg/kg ebrotidine, respectively, for 17 days. A third group of 20 rats was used as a control. Once the administration period had concluded, the animals were killed and their stomachs were removed and processed by the periodic acid-Schiff (PAS) histochemical method, selective for mucopolysaccharides. PAS-positive areas exhibited a characteristic carmine colour, allowing morphometric study by computerized image analysis. All the histological sections studied were from the same region of the stomach. A significant increase in the PAS-positive area corresponding to glandular mucus was found in all treated groups. This action is consistent with an increased secretion of mucopolysaccharides and represents one of the main mechanisms of the cytoprotective action of ebrotidine.