The protective effects of specific duodenal mucosal extracts, as well as of intraduodenal olive oil, against ulceration in the ulcerogenic preparation used by Shay et al. were studied. Both the intraduodenal oils and intravenous administration of the specific mucosal extracts were effective in preventing the occurrence of the gastric lesions produced by pyloric ligation for 20 hours in fasting rats. The anti-ulcer efficacy was most marked by olive oil, Vitrum secretin or Boots pancreozymin and was least with mineral oil or Boots secretin. The acidity and pepsin content of gastric juice determined 5 hours after pyloric ligature in fasting rats was significantly decreased by olive oil and by the specific extract except the Boots secretin. These results suggested that the specific duodenal mucosal extracts are probably enterogastrone liberated by fat in the duodenum. It is not explained why intraduodenal mineral oil has some effect in preventing the ulcerative lesions. The mineral oil induced a suppression of pepsin content along with an increase of acid content in the juice. Intraduodenal acid was also slightly effective and alkali was ineffective in prevention of gastric lesions. However in both groups the acid and pepsin contents were not low. Pretreatment with atropine, hexamethonium or acetazolamide was moderately effective in preventing the ulceration. Acetazolamide showed a marked increase in pepsin and a decrease in acid content of gastric juice.