Intravenous administration of 5-hydroxytryptamine (5-HT) produced a depressor effect on pyloric pressure and an increase in the duration of this depressor effect on gastric pressure dose-dependently in anesthetized rats. Pretreatment with a selective 5-HT3-receptor antagonist, ICS 205-930 (10 micrograms/kg), inhibited these effects. Intravenous administration of 5-HT produced a dose-dependent increase in efferent gastric vagus nerve activity (GVNA). A selective 5-HT3-receptor agonist, 2-methyl-5-HT, also produced a dose-dependent increase in GVNA. Pretreatment with a selective 5-HT3-receptor antagonist, ICS 205-930 (10 micrograms/kg), caused a shift to the right in both the 5-HT and 2-methyl-5-HT dose-response curves. These findings suggest that exogenous 5-HT activates efferent vagus gastric nerve activity and may trigger or mediate the gastric motility via 5-HT3-receptors.