Urocortin (UCN) is a new mammalian member of the corticotropin releasing factor (CRF) family and supposed to be an endogenous ligand for type 2 CRF receptors. Previous studies have revealed that UCN mRNA exists in the supraoptic nucleus (SON), and that water deprivation increases UCN immunoreactivity in SON. In this study, we examined the effect of centrally-administered UCN on arginine vasopressin (AVP) release in conscious rats. Intracerebroventricular (i.c.v.) injection of UCN (5.0 microg/rat) significantly attenuated AVP release induced by hyperosmolality at 30 min after the injection. In contrast, CRF (5.0 microg/rat) injected i.c.v. had no significant effect on AVP release. These results suggest that central UCN play an inhibitory role in osmoregulation of AVP release.