Activation of peripheral serotonin (5-HT) receptors, classified as 5-HT3, was shown to elicit the pharyngeal reflex in anesthetized rats. Intravenous bolus injection of 5-HT (6.25-50 micrograms/kg) evoked rhythmic bursts in the efferent pharyngeal branch of the vagus nerve in a dose-related manner, whereas afferent superior laryngeal nerve activity was not altered by even a high dose of 5-HT. The pharyngeal branch response was blocked by pretreatment with a selective 5-HT3-receptor antagonist YM060 (1 and 10 micrograms/kg). A 5-HT3-receptor agonist, 2-methyl-5-HT, also produced a rhythmic burst in the pharyngeal branch, and this effect was blocked by YM060. Intrapharyngeal pressure was rhythmically increased by both 5-HT (12.5-50 micrograms/kg) and 2-methyl-5-HT (6.25-50 micrograms/kg) in a dose-related manner. Both of these effects were antagonized by YM060 (10 micrograms/kg). In addition, a neuromuscular blocking agent vecuronium (1 mg/kg iv) completely inhibited the 5-HT-induced increase in pharyngeal pressure. After a bilateral vagotomy was performed below the nodose ganglia, the 5-HT-induced increase in pharyngeal branch activity was abolished, whereas a bilateral sectioning of the superior laryngeal nerve did not alter the 5-HT-induced increase in pharyngeal branch activity. Retrograde tracing with fluorescent dye (fast blue) was used to identify the cell bodies of the pharyngeal branch. Pharyngeal motoneuron cell bodies were distributed along the entire length of the nucleus ambiguus. Our results suggest that exogenous 5-HT-induced increases in pharyngeal branch activity and intrapharyngeal pressure may be initiated by the peripheral 5-HT3-receptors of the vagal nervous system and that this may be a viscerosomatic reflex.