Oxytocin is released within the supraoptic nucleus during parturition and suckling. During suckling, such release is important in positive feedback stimulation of oxytocin neurons. We have investigated whether oxytocin released within this hypothalamic nucleus during parturition (1) acts on local receptors to further amplify its own release in a positive feedback manner and (2) is critically involved in the regulation of the delivery process. To examine the effect of the oxytocin antagonist on oxytocin release within the supraoptic nucleus, microdialysates were sampled before and during parturition and either vehicle or the antagonist was infused adjacent to the microdialysis probe directly into the supraoptic nucleus after delivery of the second pup. Intranuclear infusion of an oxytocin receptor antagonist (des-Gly-NH2d(CH2)5[Tyr(Me)2Thr4]OVT; 50 ng/0.5 microliters) significantly (P < 0.01) diminished the parturition-related rise in oxytocin release within the supraoptic nucleus and reduced the number of pups delivered during the first and second 30-min dialysis period compared to vehicle-treated controls. Bilateral infusion of the oxytocin receptor antagonist into the supraoptic nucleus after delivery of the second pup significantly slowed parturition (P < 0.05), although the parturition-related rise in plasma oxytocin concentration was unchanged. In addition, the onset of suckling was significantly affected by the antagonist as indicated by fewer liver pups and fewer surviving pups with milk in their stomachs 24 hours after parturition (P < 0.05). To seek other, periventricular sites of oxytocin action during parturition, oxytocin or the oxytocin antagonist was infused into the lateral cerebral ventricle from the birth of pup 2. Via this route, oxytocin speeded up parturition, but the antagonist was ineffective; thus it appears that periventricular oxytocin-sensitive sites are not normally active in promoting parturition, and can do so. The findings indicate a receptor-mediated positive feedback action of oxytocin on its own release within the supraoptic nucleus during parturition, which seems to be involved in the progress of parturition without significantly affecting circulation oxytocin levels. Oxytocin released within the supraoptic nucleus might be important for the coordinated activation of oxytocin neurons and for the synergistic central and peripheral oxytocin effects involved in the regulation of parturition-related events necessary for the survival of the newborn, including the onset of lactation.