Dietary mehaden oil enhances mucosal hyperplasia that normally occurs after massive small bowel resection. In contrast, dexamethasone and aspirin inhibit the adaptation response. In order to gain insight on the mechanism of these effects, male Sprague-Dawley rats weighing approximately 150gram were randomly divided into two groups and fed diet containing either 15% safflower oil or 14% menhaden oil and 1% safflower oil. Ten days later they were subjected to 70% jejunoilear resection. Immediately after surgery each group was further divided into two groups and receive either vehicle or 125ug/kg/day dexamethasone subcutaneously. All animals were sacrificed seven days after the surgery, and the remaining intestine was removed and divided at the anastomotic site. Dexamethasone, which decreased gut hyperplasia in both dietary groups, decreased both serum IGF-I levels and ileral PGE2 synthesis. Menhaden oil enhanced gut hyperplasia, but did not increase IGF-I or IGF-II levels in serum. PGE2 synthesis was lower in the ileum of menhaden oil-fed rats compared to that of safflower oil-fed rats. The effects of menhaden oil on adaptation did not apper to be mediated either through IGFs or PGE2 synthesis. Other factors could have played a role in enhancing adaptation following menhaden oil feeding.