Urocortin (UCN) is a recently isolated 40 amino acid-containing neuropeptide that is the second endogenous mammalian ligand for the corticotropin-releasing factor (CRF) receptors. While UCN and CRF both display a similar high affinity for the CRF(1) receptor, the affinity of UCN for the CRF(2) receptor is more than 10-fold higher than that of rat/human CRF. UCN mRNA expression is highest in the Edinger-Westphal nucleus and lateral superior olive, with the most prominent terminal fields found in the lateral septum. Because of the higher relative affinity of UCN for the CRF(2) receptor and the corresponding neuroanatomical distribution of the highest density of UCN expression and innervation to brain regions preferentially expressing the CRF(2) receptor subtype, it has been hypothesized that UCN is the preferred endogenous ligand for the CRF(2) receptor. Following central administration, UCN has been demonstrated to produce behavioral and physiological effects that are qualitatively similar to CRF. Quantitatively, however, UCN appears to be a more potent suppressor of ingestive behavior (food and water intake) and a less potent inducer of anxiogenic behavior than CRF.