Hyperosmotic solutions of xylitol exhibited significant antiulcer activity in the rat at osmotic concentrations (1000 mOs/1) which were devoid of antisecretory effect. The same solutions also protected the rat gastric mucosa against indomethacin and stress-induced erosions, and the protection was unaffected by the addition of 0.15 N HCl. Moreover, hyperosmotic solutions by xylitol, sorbitol or NaCl were protective against the necrotizing effect of NaOH (0.2 N) in a concentration-dependent manner. The cytoprotective action exerted by hyperosmotic solutions of xylitol against the NaOH-induced erosions was abolished, in a dose-dependent fashion, by pretreatment with the cyclooxygenase inhibitor indomethacin. It is concluded that in experimental ulcer models, in which the capacity of the mucosa to synthetize PG is unimpaired, the increased biosynthesis of prostaglandins resulting from exposure to hyperosmotic solutions may be crucial in the cytoprotective effect of the latter.