Intracellular recordings were obtained from vagal neurons and their response to oxytocin was investigated in slices from the rat and the guinea pig brainstem. After recording, Lucifer yellow was injected into the cells to verify their localization within the dorsal motor nucleus of the vagus nerve (dmnX). In the rat, virtually all neurons throughout the rostrocaudal extent of the dmnX increased their rate of firing in the presence of 10-1000 nM oxytocin and their membrane depolarized in a reversible concentration-dependent manner. This excitation was probably exerted directly on the impaled cells rather than being synaptically mediated, since it persisted in a low calcium/high magnesium medium or in the presence of tetrodotoxin. These data provide evidence for a direct membrane effect of oxytocin on a defined population of neurons in the rat brain. In the guinea pig, vagal neurons were fired by glutamate but were not excited by oxytocin, even though we detected many more oxytocin-immunoreactive structures in the guinea pig dmnX than in the rat dmnX. Therefore, homologous nuclei in the brains of two closely related mammals differ markedly in the density of oxytocinergic axons they contain. Unexpectedly, the magnitude of the electrophysiological effects of oxytocin on vagal neurons appeared inversely related to the amount of oxytocin-like immunoreactivity present in dmnX.