To determine whether the release of newly formed mediators such as the peptidoleukotrienes and platelet-activating factor might modulate the food protein induced jejunal smooth muscle contraction observed in sensitized rats, Hooded–Lister rats were sensitized by injection of ovalbumin (10 μg i.p.) and controls were sham sensitized with saline. Fourteen days later the contractility of longitudinally (n = 9) and circularly (n = 9) oriented jejunal segments (mucosa intact) were examined in standard tissue baths in response to antigen, leukotrienes, and platelet-activating factor alone and in the presence of a specific leukotriene receptor antagonist (MK-571), a 5-lipoxygenase inhibitor (L651,392), and a platelet-activating factor receptor antagonist (WEB 2086). Although the responses of control and sensitized tissues to stretch and 10−4 M bethanechol were similar, only sensitized tissues contracted in response to antigen (1 mg/mL). MK-571 (10−5 M) reduced or significantly inhibited the contractile response of sensitized longitudinally and circularly oriented tissues to 10−7 M leukotrienes C4, D4, or E4, but neither L651,392 (10−4 M) nor MK-571 (10−5 M) significantly reduced the contractile response of sensitized tissues to antigen challenge. WEB 2086 (10−4 M) significantly (p < 0.01) reduced the contractile response of sensitized longitudinally and circularly oriented tissues to 10−7 M platelet-activating factor but did not significantly alter the response to antigen in longitudinally (45% of control, p = 0.14) or circularly (118% of control, ns) oriented jejunal smooth muscle. In this model leukotrienes and platelet-activating factor play an insignificant role in modulating food protein induced jejunal smooth muscle contraction in intestinal anaphylaxis.Key words: leukotrienes, platelet-activating factor, smooth muscle, anaphylaxis, food allergy.