The role of corticotrophin-releasing factor (CRF) and prostaglandin in interleukin-1β (IL-1β)-induced delayed gastric emptying was investigated. Gastric emptying was monitored 20 min after orogastric delivery of a methylcellulose phenol red solution in fasted rats injected intravenously with IL-1β at the ED50 38, CαMeLeu37]-CRF12-41 (20 μg/rat), injected intracisternally, or indomethacin (5 mg/kg i.p.) completely abolished IL-1β (3 ng/rat i.v.)-induced gastric stasis. The CRF antagonist injected intravenously (20 μg/rat) did not influence the IL-1β inhibitory action. None of the pretreatments given alone influenced basal gastric emptying. These data suggest that peripheral IL-1β-induced inhibition of gastric emptying is mediated by specific IL-1 receptor interactions and brain CRF pathways requiring the integrity of eicosanoid-cyclooxygenas