The mammalian gallbladder mucosa is lined by a simple columnar epithelium. Typical surface epithelial cells (principal cells) contain short microvilli, secretory granules, dense bodies, mitochondria and Golgi apparatus. Dense bodies are thought to be lysosomes. Secretory granules contain mucous glycoproteins which are released to the lumen by exocytosis. Oligosaccharide side chains of mucous glycoproteins may provide a favorable environment for nucleation of cholesterol in gallstone formation; therefore they have been studied during the past decades. Histochemical techniques allow the in situ identification of carbohydrates at both the cellular and subcellular levels. The oligosaccharide chains of principal cell mucous glycoproteins have been studied by classical histochemical techniques (PAS, alcian blue, HID, etc). These techniques indicate that mammalian gallbladder mucous glycoproteins are heavily sulphated, whereas sialic acid residues are scarce. Neutral mucins have not been described in the mammalian gallbladder. Electron microscopic studies have located the oligosaccharide chains in secretory granules and Golgi apparatus. More recently, lectins (molecules which specifically recognize and bind with different saccharides or saccharide sequences) have been applied for the intracellular localization of carbohydrate residues. Lectin histochemistry has detected fucose, galactose, N-acetylglucosamine, N-acetylgalactosamine and N-acetylneuraminic acid residues in mucous granules, Golgi apparatus and apical membrane of human principal cells. Mannose residues were observed only in dense bodies. The combined use of deglycosylation procedures and lectin histochemistry has revealed a variety of terminal sequences in oligosaccharide chains of gallbladder mucous glycoproteins: Neu5Ac(alpha 2-3)Gal(beta 1-3)GalNAc, Neu5Ac(alpha 2-3)Gal(beta 1-4)GlcNAc and Gal(beta 1-4)GlcNAc. This technology also suggested the occurrence of N-linked oligosaccharides in the dense bodies of principal cells. Mucous granules mainly contained mucin-type O-linked oligosaccharides although some N-linked chains have also been detected. Gallstone formation is probably a complex process depending on multiple factors. Mucous glycoproteins are one of the factors involved in this process. Histochemical methods offer an excellent research tool for the characterization of glycoproteins in the epithelial cells of the gallbladder, thus contributing to the elucidation of the pathophysiology of gallstone formation.