The neural mechanisms involved in mediation of the inhibitory effects of ethanol on the gastric emptying and the small intestinal transit were studied in adult male rats. The gastrointestinal transit was determined by measuring the amount of phenol red recovered from the stomach and small intestine after intragastric administration. Spinal and/or vagal peptidergic afferent nerves were subjected to selective denervation by chemodenervation techniques using capsaicin, a potent and specific sensory neurotoxin. Intragastric administration of a 2.5 g/kg body weight dose of ethanol resulted in inhibition of the gastric emptying and the small intestinal transit. Prior systemic treatment with capsaicin, which defunctionalizes both spinal and vagal capsaicin-sensitive afferent nerves, abolished the inhibitory effect of ethanol on the gastrointestinal transit. Similarly, selective chemodenervation of the vagal afferents by perineural capsaicin treatment completely blocked the effect of ethanol. These observations furnish evidence indicative of the involvement of capsaicin-sensitive neural pathways, and in particular vagal afferent nerves, in the mediation of the inhibitory effect of large doses of ethanol on the gastrointestinal motility.