The hypothesis that the elements essential for the induction of acute cholecystitis are the presence of lithogenic bile and cystic duct occlusion was tested in the prairie dog gallstone model. Neither the presence of gallstones alone nor acute cystic duct occlusion alone resulted in acute inflammation of the gallbladder. Acute cholecystitis developed in prairie dog gallbladders containing cholesterol-saturated bile, with or without gallstones, shortly after cystic duct occlusion. These data suggest that the factors essential for the induction of acute cholecystitis are the presence of lithogenic bile and cystic duct occlusion and that gallstones, although frequently present, are not an essential prerequisite to acute inflammation.