This study describes the cloning and characterization of urocortin II (Ucn II), a new member of the corticotropin-releasing factor (CRF) neuropeptide family. Ucn II is selectively bound by type 2 CRF receptors (CRF-R2) and is expressed in discrete regions of the rodent central nervous system, including stress-related cell groups in the hypothalamus and brainstem. Central administration of Ucn II elicits activation responses in a core circuitry subserving autonomic and neuroendocrine regulation, but its overall pattern does not closely match the distribution of CRF-R2. Behaviorally, Ucn II attenuates nighttime feeding without affecting gross motor activity. These findings suggest that Ucn II plays a role in central autonomic and appetitive control but not in generalized behavioral activation. The identification of Ucn II as a CRF-R2-selective ligand will facilitate further investigation into the roles of individual CRF-related signaling molecules in stress-related physiologic and behavioral functions.This study describes the cloning and characterization of urocortin II (Ucn II), a new member of the corticotropin-releasing factor (CRF) neuropeptide family. Ucn II is selectively bound by type 2 CRF receptors (CRF-R2) and is expressed in discrete regions of the rodent central nervous system, including stress-related cell groups in the hypothalamus and brainstem. Central administration of Ucn II elicits activation responses in a core circuitry subserving autonomic and neuroendocrine regulation, but its overall pattern does not closely match the distribution of CRF-R2. Behaviorally, Ucn II attenuates nighttime feeding without affecting gross motor activity. These findings suggest that Ucn II plays a role in central autonomic and appetitive control but not in generalized behavioral activation. The identification of Ucn II as a CRF-R2-selective ligand will facilitate further investigation into the roles of individual CRF-related signaling molecules in stress-related physiologic and behavioral functions.