Acute inflammation of the intestine is associated with motility changes. We investigated the acute effect of inflammatory mediators such as interleukin-1β, interleukin-2 and tumor necrosis factor-α (TNF-α) on electrically stimulated ascending and descending reflex responses of the rat small intestine. Exogenous application of interleukin-1β caused a concentration-dependent inhibition of the oral contraction (0.1 ng/ml: -22.9+/-3.8%, 10 ng/ml: -57.0+/-7.4%, P<0.05, n=10) but had no effect on anal relaxation. The interleukin-1 receptor antagonist alone had no significant effect on the reflex response, but prevented the inhibitory effect of interleukin-1β (10 ng/ml: -3.9+/-11.4%, n=8). Interleukin-2 and TNF-α had no significant effect on the oral contractile and the anal inhibitory response (n.s., n=10). Using reverse transcriptase polymerase chain reaction (RT-PCR) the presence of mRNA of the interleukin-1 receptor was demonstrated in the rat small intestine. Preincubation of the preparation with indomethacin (10 - 6 M), the histamine H 1 receptor antagonist, pyrilamine (10 - 8 M), and the histamine H 3 receptor antagonist, clobenpropit (10 - 8 M), decreased the oral contraction by 60.1+/-7.7%, 42.8+/-6.9% and 44.4+/-14.2% as well as the anal relaxation. These data suggest that acute administration of interleukin-1β inhibits the ascending and descending contractile reflex pathway and this effect seems not to be mediated by prostaglandins or histamine receptors.