This study was undertaken to determine the effects of 5-hydroxytryptamine (5-HT) on vagal mucosal afferent endings and how this may relate to their sensitivity to other stimuli. Single afferent fibres with receptive fields in the mucosa of the upper gastrointestinal tract were recorded from the cervical vagus of Urethane anaesthetized ferrets. The selection criteria included failure to respond to luminal distension (i.e., vagal tension receptors were excluded). All fibres tested responded to mucosal stroking. The majority of these (28/32) also responded to close-intrarterially applied 5-HT (10 micrograms) with a brief burst (usually < 15 s) of action potentials, which in 6/6 cases was reduced or abolished by the 5-HT3 receptor antagonist granisetron (0.1-0.5 mg/kg i.v.), as were four responses to cholecystokinin-octapeptide (100-400 pmol close I.A.). The response to 5-HT was shown to be dose-dependent over the dose range 2-75 micrograms on six occasions. Responses to luminal stimuli, which included 150 mM HCl, 1 M NaCl, and mucosal stroking, were not blocked by granisetron although in three fibres, the resting discharge was reduced by the antagonist, suggesting that resting discharge in vagal mucosal afferents may be influenced by endogenously released 5-HT.