Sulglycotide, a well known antisecretory and antiulcer compound, has been further investigated for its ability to protect rat gastric mucosa against extensive necrosis induced by absolute ethanol, NaOH (0.2N) and NaCl (30%). Sulglycotide, which has been compared with cimetidine, displays a dose-dependent cytoprotective activity against the above necrotizing agents. The results obtained indicate that Sulglycotide requires a normal prostaglandin biosynthetic process in order to manifest its antiulcer activity. In fact gastric mucosa from animals treated with Sulglycotide releases in vitro a greater amount of PGl2-like activity; and furthermore no protection was observed against gastric lesions induced by indomethacin. As far as the mode of action of Sulglycotide is concerned it is tempting to speculate that the compound may interfere with prostaglandin degradation or it may trigger an adaptive cytoprotection which is important in maintaining the cellular integrity of rat gastric mucosa.