The present study evaluated the extent of dysfunction of the 5-hydroxytryptaminergic system in inflamed (distal colon) and noninflamed segments (jejunum and ileum) after intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in the rat. Dexamethasone was administered to control rats and TNBS-treated animals before and for 7 days after TNBS treatment. Tissue levels of 5-hydroxytryptamine (5-HT) in the inflamed colon were higher than in controls. The density of mast cells was also markedly increased. Treatment with dexamethasone attenuated the inflammatory response but did not prevent the increase in colonic 5-HT. In the noninflamed jejunum and terminal ileum, 5-HT tissue levels were markedly increased, but treatment with dexamethasone prevented this increase. It is concluded that the increase in 5-HT levels in the inflamed colon in TNBS-induced colitis may result from mast cell infiltration. In the noninflamed intestine, 5-HT tissue levels were also increased, favoring the view of a generalized mast cell infiltration.