The abnormalities of gallbladder epithelial function involved in cholesterol gallstone pathogenesis are: 1) the impaired biliary lipid absorption and 2) an increased secretion of mucin gel. We developed a model of isolated in vitro intra-arterially perfused gallbladder and showed that the normal gallbladder epithelium absorbs high amounts of biliary cholesterol and phosphatidylcholine in a proportion determined by their molar ratio in the bile which enters the lumen. This physiological lipid absorption continuously reduces biliary cholesterol molar percentage in the gallbladder lumen and protects from gallstone formation by inhibiting cholesterol crystal precipitation. On the opposite, in the presence of cholesterol gallstone disease, even if the gallbladder epithelium is hyperplastic and hypertrophic, it absorbs cholesterol and phosphatidylcholine less efficiently and cholesterol crystal precipitation is favoured. Indirect evidence exists that the impaired gallbladder lipid absorption in cholesterol gallstone disease is not caused by inflammation and is not secondary to the presence of stones. The impaired mucosal function could be the consequence of excessive chronic enrichment of hepatic bile which enters the gallbladder. The mucin gel is the only biliary protein with an established pathogenetic role in cholesterol gallstone disease. The mucin gel is thought to favour gallstone formation by promoting cholesterol crystal precipitation and aggregation.