The corticotropin-releasing hormone (CRH) system, consisting of CRH and the homologue neuropeptide urocortin together with their receptors CRH(1) and CRH(2) and a specific binding protein (CRH-BP), holds the main role in mediating the response to stressful stimuli. Besides their expression in the brain, CRH peptides and receptors have been found in multiple peripheral sites. Here we investigate the expression of CRH, urocortin, CRH receptors, and CRH-BP in the wall of human normal and inflamed gallbladders, using RT-PCR and immunohistochemistry. Urocortin, but not CRH gene transcripts, was detected in RNA isolated from human gallbladder biopsy specimens. Urocortin immunoreactivity was localized in epithelial cells of the gallbladder mucosa. Gene expression of CRH(2) receptor was also detected, and the receptor protein had a localization similar to that of urocortin. Finally, CRH-BP gene expression and low levels of protein immunoreactivity were also shown. There were no differences in the expression profiles of all the above molecules between normal and inflamed tissues. In conclusion, the CRH system is present in the human gallbladder, urocortin being the major ligand expressed, possibly exerting an autocrine/paracrine biological role via activation of the CRH(2(alpha)) receptors found locally. Further study is required to enfold the biological role of these effectors in gallbladder physiology and pathogenesis.