In the present study, we investigated the role of central calcitonin gene-related peptide (CGRP) and amylin receptors in mediating the anorectic effects of CGRP and amylin in rats chronically cannulated in the lateral brain ventricle. Intracerebroventricular (ICV) injection of the CGRP and amylin receptor antagonist CGRP(8-37) failed to influence the anorectic effects of peripherally injected CGRP and amylin. CGRP(8-37) alone, however, increased food intake in food deprived rats when administered 2 h before food presentation. Under the same experimental conditions, the more specific amylin receptor antagonists amylin(8-37) or AC 187 did not affect food intake. We therefore conclude, that CGRP is a physiological regulator of food intake within the central nervous system, acting at central CGRP receptors. Peripheral receptors, however, are likely to mediate the anorectic effects of peripherally administered amylin and CGRP.