We found that beta-lactotensin (His-Ile-Arg-Leu), which has been isolated as an ileum-contracting peptide from chymotrypsin digest of bovine beta-lactoglobulin, dose-dependently suppresses food intake after intracerebroventricular (i.c.v.) or intraperitoneal administration at a dose of 40 nmol/mouse or 100mg/kg, respectively, in fasted mice. Orally administered beta-lactotensin also suppressed food intake at 500 mg/kg. We previously reported that beta-lactotensin acts as an agonist for neurotensin receptors; however, the anorexigenic activity of beta-lactotensin was not inhibited by i.c.v. co-administration with SR48692 or levocabastine, an antagonist for neurotensin NT(1) or NT(2) receptor, respectively. On the other hand, the anorexigenic effect of beta-lactotensin was blocked by i.c.v. co-administration with astressin or calcitonin gene-related peptide (CGRP)(8-37), an antagonist for corticotropin releasing factor (CRF) or CGRP, respectively. beta-Lactotensin had affinity for neither CRF nor CGRP receptor. In addition, CRF-induced anorexigenic activity after i.c.v. administration was completely blocked by CGRP(8-37), while CGRP-induced anorexigenic activity was not inhibited by astressin. These results suggest that the CGRP system is activated downstream of the CRF system in food intake regulation. Taken together, beta-lactotensin may suppress food intake by activating the CRF system followed by the CGRP system, independently of the neurotensin system.