A vast number of intensive studies have been undertaken to clarify the mechanisms of energy balance. This study was undertaken to investigate the effect of urocortin, an endogenous ligand for corticotropin-releasing factor (CRF) type 2 receptor, on oxygen consumption in lean and genetically obese (ob/ob) mice. Oxygen consumption was measured after intraperitoneal injection in unrestrained mice at an environmental temperature of 22 degrees C of one of the following: urocortin, deamidated form of urocortin (urocortin OH) or CRF. The intraperitoneal injection of urocortin (0.3-3 nmol) dose-dependently decreased oxygen consumption in lean mice. The inhibitory effect induced by urocortin was more potent than that induced by CRF or urocortin OH. The ranking potency was urocortin > urocortin OH > CRF. Urocortin significantly reduced oxygen consumption in ob/ob mice as well as in lean mice. These results suggest that urocortin decreases oxygen consumption, and that the CRF type 2 receptor may influence energy balance in lean and ob/ob mice.