The gastric cytoprotective action of prostaglandin E2 (PGE2) and sofalcone was studied in rats. The in vitro incorporating activity of 3H-glucosamine into the gastric macromolecular glycoproteins was examined when PGE2 (0.1 mg/kg, p.o.) or sofalcone (100 mg/kg, i.p.) was administered 5, 15 or 30 min before the oral administration of absolute ethanol. The cytoprotective effect of PGE2 against gastric mucosal damage was demonstrated 5 min after PGE2 was given orally. The cytoprotective effect by sofalcone was seen after 15 min. However, during this period, the decrease in gastric macromolecular glycoprotein synthesis induced by the ethanol damage could not be restored by pretreatment with PGE2 or sofalcone. On the other hand, the reduction in the content of the gastric macromolecular glycoproteins by the ethanol damage was found to be prevented to a significant extent by pretreatment with PGE2. The same phenomenon was also observed in the administration of sofalcone. Accordingly, PGE2 has stimulating effect on the gastric glycoproteins biosynthesis, but this effect can not be considered as the mechanism responsible for cytoprotection, if indeed a single mechanism exists. Thus, it is suggested that the adhesion or maintenance of secreted macromolecular glycoproteins to the gastric tissue is closely related to cytoprotection.