The wall of the rat common bile duct (CBD) consists of several epithelial ducts embedded in connective tissue which contains some regions with cells weakly stained by an antibody against alpha smooth muscle actin. The hepatic side (HS) is more vascularized than the duodenal side (DS). Calcitonin gene-related peptide (CGRP)-like immunoreactivity is present in nerve fibres penetrating deeply into the CBD wall. On whole-mount preparations, CGRP innervation is mainly associated with blood vessels in the HS, whereas it forms a wide meshed network independent of vasculature in the DS. Abundance of CGRP innervation was compared between both sexes and at different ages. No differences were found in the total number of fibres between males and females except at 4 months of age, when males had statistically more abundant innervation than females. However, during aging, while the abundance of innervation (fibers/mm) remained stable in both HS and DS in females, it significantly decreased in males. Autoradiography demonstrated the presence of I-125-CGRP binding sites in the rat CBD. Iii vitro, 30% of HS strips showed spontaneous rhythmic contractions but all the strips (autocontractile or not) contracted dose dependently in response to acetylcholine (Ach) or substance P (SP). However, DS strips were neither autocontractile nor responsive to Ach or SP. Perfusion of all strips with 10(-7) M CGRP produced no effects nor influenced Ach- or SP-induced contractions. (C) 1995 Academic Press, Inc.