The purpose of the present study was to determine whether feeding stimulates prostaglandin (PG) synthesis in the gastric mucosa and whether this might play a role in the defensive mechanism of the gastric mucosa. The effect of refeeding on the formation of gastric lesions induced by nonsteroidal antiinflammatory drugs and on the generation of prostaglandin in the gastric mucosa was investigated. In the fasted rat aspirin and indomethacin produced many lesions in the corpus, but few or no lesions in the antrum. Refeeding of chow pellets before aspirin or indomethacin significantly decreased the corpus lesions, but provoked lesions in the antrum. When each drug was given before the refeeding, the protection against corpus lesions by refeeding was reduced and the lesions in the antrum were significantly increased. Mucosal generation of 6-keto-PGF 1 alpha (a stable metabolite of PGI2) and PGF2 alpha was measured ex vivo by the method of Whittle. The generation of 6-keto-PGF1 alpha and PGF2 alpha in the fasted rat deprived of food for 24 hr was 1761 +/- 170 and 217 +/- 7 ng/min/g tissue in the corpus mucosa, and 2958 +/- 217 and 453 +/- 33 ng/min/g tissue in the antral mucosa, respectively. Refeeding of chow pellets significantly increased the generation of both prostaglandins in the antral mucosa and of PGF2 alpha in the corpus mucosa, but did not affect the generation of PGI2 in the corpus mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)