The present study was performed to investigate the influence of the chemical stimulation of medullary raphe nuclei by the stable TRH (thyrotropin-releasing hormone) analog, RX 77368, on gastric contractility. Urethane-anesthetized rats were acutely implanted with miniature strain gauge force transducers on the corpus of the stomach for continuous recording of gastric contractility. Traces were analyzed by computer. Microinjections of vehicle or RX 77368 into the raphe pallidus or raphe obscurus were performed using pressure injection of 50 nl through glass micropipettes 30 min following basal recording of gastric contractility. RX 77368 (0.7-77 pmol) dose dependently stimulated gastric contractility when microinjected into the raphe pallidus and raphe obscurus. The stimulation of gastric contractions induced by microinjection of RX 77368 (77 pmol) into these raphe nuclei was completely blocked by vagotomy and prevented (raphe obscurus) or reduced (raphe pallidus) by atropine. RX 77368 (7.7-77 pmol) microinjected into the inferior olive, pyramidal tract, medial lemiscus was ineffective. These results demonstrate that chemical stimulation of the raphe pallidus and obscurus by RX 77368 stimulates gastric contractility through vagal and muscarinic pathways. These data suggest a role for medullary raphe nuclei in the central vagal regulation of gastric contractility.