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Effects of 16-16-dimethyl-prostaglandin E2 (PGE2), cimetidine (CIM) and geranyl-geranylacetone (GGA) on acetyl salicylic acid (ASA) or taurocholic acid (TCA) induced-gastric mucosal damage were investigated in the rat gastric chamber. PGE2, CIM and GGA significantly inhibited the decrease of potential difference of gastric mucosa caused by ASA or TCA. They also depressed the increase of ion flux of H + and Na + in ASA or TCA-induced gastric mucosal damage. Electron microscopic study revealed that PGE2 CIM and GGA reduced the changes of junctional complexes of gastric surface mucous cells induced by ASA or TCA. Results of these experiments indicate that PGE2, CIM and GGA protect the rat gastric mucosa from the damage caused by ASA or TCA and that their influences on the junctional complexes of gastric surface mucous cells might contribute to these protective effects.