A combined microdialysis/microinfusion technique was used to investigate whether arginine vasopressin (AVP) is involved in the regulation of its own release into the extracellular fluid of the supraoptic nucleus in vivo. While intranuclear neuropeptide release was monitored, 0.33 microliter of either vehicle, lysine vasopressin (LVP; 10 ng microliters -1) or a V1/V2 AVP receptor antagonist (100 ng microliters -1) was infused into the supraoptic nucleus of adult male Wistar rats before and during direct osmotic stimulation of the nucleus via the microdialysis probe. Administration of LVP increased basal AVP release, whereas administration of the V1/V2 receptor antagonist attenuated the increase in AVP release during osmotic stimulation observed in vehicle-treated controls. Taken together, these results indicate a receptor-mediated positive feedback action of endogenous AVP on its own release within the supraoptic nucleus.