Fluid transport of the gallbladder has been studied in two models of experimental cholelithiasis: dihydrocholesterol-induced gallstones in the rabbit and lincomycin-induced gallstones in the guinea pig. Using the noneverted explained gallbladder of the rabbit and the guinea pig, the transport of luminal to serosal fluid has been quantitated before, during, and after stone formation. The everted gallbladder preparation of the rabbit has also been used to measure fluid transport before and during gallstone formation. In both models, an increased fluid transport was observed in the phase of gallstone induction and a return to normal after stones were formed. This abnormality preceded the appearance of conventional histological features of cholecystitis. There was also a coincidental increase in glycoprotein production from and cell proliferation of the gallbladder epithelium. This enhancement of fluid transfer may play a contributing role in the genesis of gallstones.