The present study characterizes the nature of the response to the platelet-activating factor (PAF) in isolated gastric corpus with and without mucosa. PAF (10(-8) M) induced contraction of rat isolated gastric corpus strips followed by desensitization of this tissue. Incubation of strips with the specific PAF-receptor antagonist WEB 2086 (5 x 10(-8) -5 x 10(-5) M) the prostaglandin blocker indomethacin (10(-6) M) and the 5-hydroxytryptamine antagonist methysergide (10(-5) M) reduced significantly the contraction induced by PAF. Neither of the histamine H1/H2 antagonists diphenhydramine (10(-6) M) or cimetidine (10(-5) M) affected the contraction induced by PAF. In contrast with the whole gastric corpus, in mucosa-free strips, the contractile effect of PAF was not modified by methysergide. The present study supports the view that the effect of PAF is mediated by activation of specific PAF receptors and the release of prostaglandins and 5-hydroxytryptamine in isolated gastric corpus. Furthermore, our results suggest a role of the gastric mucosa via the release of 5-hydroxytryptamine which contributes to the contractile effect of PAF in the gastric smooth muscle.