Leptin is a key afferent signal that decreases food intake and increases energy expenditure by acting on the specific receptors in the hypothalamus. Corticotropin-releasing hormone (CRH) and its homologous peptide, urocortin, are also known to have a potent anorectic effect when given intracranially. To determine possible involvement of these two peptides in the leptin-induced anorexia, in the present study, food intake was measured in rats pretreated with antibodies against CRH and urocortin. In the control rats without antibody pretreatment, intracerebroventricular (icv) injection of leptin (0.1-1 microg/rat) suppressed nocturnal food intake. The anorectic effect of leptin was substantially attenuated in rats pretreated with icv injection of an anti-CRH antibody, but not with an anti-urocortin antibody. These results suggest that the anorectic effect of leptin is mediated by CRH, but not by urocortin, in the hypothalamus.