The area of the ventromedial nucleus of the hypothalamus in the guinea-pig was shown in autoradiographs to contain high affinity binding sites for oxytocin. In order to ascertain whether these sites may represent neuronal receptors, single-cell extracellular recordings were obtained from ventromedial neurons in coronal slices of t h e hypothalamus of adult guinea-pigs. Oxytocin applied in the nanomolar range excited about half of the neurons tested; none were inhibited. The response to the peptide was reversible and concentration-dependent. It was exerted directly since it persisted under t h e condition of synaptic isolation. Moreover, the effect was specific since it could be mimicked by a selective oxytocin agonist and since vasopressin was usually at least 10-fold weaker than oxytocin. These findings suggest that the binding sites for oxytocin detected by light microscopic autoradiography in the guinea-pig hypothalamic ventromedial nucleus represent functional receptors.In the rat brain, specific high affinity binding sites for oxytocin could be detected in various areas by light microscopic autoradiography, both in developing ( I ) and adult animals (2-5). In several of these areas, oxytoci?, was shown to excrt a neuronal effect ( I , 6 12), corroborating the view that binding sites detected by autoradiography represent, at least in part, functional receptors associated with neurons.Unexpectedly, when other species were examined, marked regional differences in the distribution of oxytocin binding sites were found ( 1 3). Thus, the ventral hippocampus and the dorsal motor nucleus of the vagus nerve were labelled in the rat but not in the guinea-pig (9, 11). In accordance with these autoradiographical data, electrophysiological recordings showed that neurons in the hippocampus and in the dorsal vagal nucleus of the rat were excited by oxytocin; in contrast, no neuronal sensitivity to this peptide was observed in the homologous area in the guinea-pig brain (9, 1 I).Amongst the regions of the rat brain which are most intensely labelled by [3H]oxytocin and by the radioiodinated selective oxytocin antagonist [1251]OTA (l4), is the hypothalamic ventromedial nucleus ( 1 , 4, 5). In the present study, we assessed whether the hypothalamic ventromedial nucleus also contains oxytocin binding sites in the guinea-pig. Moreover, in order to determine whether hypothalamic ventromedial neurons in this species are sensitive to oxytocin, we have carried out extracellular recordings from hypothalamic slices. The specificity of the neuronal action of oxytocin was ascertained by using a synthetic structural analogue, acting as a selective agonist (15). Part of these data have been presented a t scientific meetings (16,17).