It is unknown which neurotransmitter receptors are involved in the transfer of sensory information from the digestive tract to the brainstem. We examined the potential involvement of central glutamate, acetylcholine, and CGRP receptors in vagal pathways arising from gut chemo- and mechanosensitive afferents. Unitary recordings were made from 21 vagal preganglionic efferent neurones. Neuronal discharge showed either excitation or inhibition in response to oesophageal balloon distension (1-2 ml), gastric distension (40-60 ml in whole stomach or 20 ml in proximal stomach), cholecystokinin-8s (100 pmol close intra-arterially) and bradykinin (18 nmol close intra-arterially). Effects of glutamatergic non-NMDA, muscarinic M1, and CGRP1 receptor antagonism on efferent responses were investigated using CNQX (75-155 nmol i.c.v.), pirenzepine (2.5-5.0 micromol/kg i.v.), and hCGRP8-37 (3.2-6.4 nmol i.c.v.), respectively. CNQX, pirenzepine, and hCGRP8-37, respectively, altered efferent responses in 65%, 23% and 41% of neurones. When both CNQX and hCGRP8-37 were administered, a further 58% of responses were reduced. CNQX and hCGRP8-37 reduced a proportion of efferent responses to all stimuli whereas pirenzepine selectively reduced only efferent responses to gastric distension. We conclude that central CGRP1 and non-NMDA receptors are involved in mediating a range of upper gastrointestinal mechano- and chemo-sensitive afferent inputs onto vagal efferents. M1 receptors, on the other hand, are selectively involved in neurotransmission from gastric mechanoreceptors.