Electrical stimulation of afferents of the right cervical vagus inhibited the tail-flick reflex elicited by noxious heat in barbiturate-anesthetized rats. This inhibitory effect was eliminated in rats receiving local anesthetic blockade of either the nucleus tractus solitarii (NTS), the lateral reticular nuclei, the nucleus raphe magnus-medullary reticular formation, or nucleus raphe obscurus regions of the medulla. Similarly, the vasodepressor and bradycardic effects of vagal stimulation were either attenuated or eliminated by local anesthetic blockade of these regions. Microinjection of the non-specific glutamate antagonist γ-d-glutamylglycine (DGG) into the NTS region also eliminated vagally evoked inhibition of the tail-flick reflex, hypotension, and bradycardia. Conversely, microinjection of glutamate into the NTS region resulted in inhibition of the tail-flick reflex, hypotension, and bradycardia. These findings with DGG and glutamate are consistent with the view that glutamate serves as a neurotransmitter of the primary vagal afferents mediating these antinociceptive and cardiovascular responses. These results are discussed in terms of vagal afferent influences on somatosensory, somatomotor, and cardiovascular function. © 1988.