The inhibitory effect of central administration of calcitonin-gene related peptide (CGRP) on pancreatic secretion stimulated by bile-pancreatic juice diversion was determined in conscious rats. Rats were prepared with separate cannulae for draining bile and pancreatic juice and with a duodenal cannula and an extrajugular vein cannula. In addition, another cannula was stereotactically implanted into the left lateral cerebral ventricle. Rats were placed in restraint cages and experiments were conducted 4 d after the operation without anesthesia. An injection of CGRP (1 nmol/10 microl) into the left lateral cerebral ventricle (i.c.v.) inhibited pancreatic secretion as well as cholecystokinin (CCK) release induced by bile-pancreatic juice diversion. Intravenous infusion of alpha- and beta-adrenergic receptor antagonist, phentolamine and propranolol did not reverse the inhibition of pancreatic secretion. Intravenous infusion of CGRP did not affect pancreatic secretion or plasma CCK concentrations. The inhibitory action of central CGRP (i. c.v.) on pancreatic secretion and CCK release stimulated by bile-pancreatic juice diversion is partially mediated by an alpha-adrenergic mechanism, although its precise mechanism has not been elucidated.