Recent studies probing the pathogenesis of biliary pancreatitis using models in experimental animals are reviewed. These studies have suggested that the earliest changes in pancreatitis involve acinar cells. These changes result in intra-acinar cell activation of digestive enzyme zymogens. Synthesis of digestive enzyme zymogens is not altered during the early stages of pancreatitis but secretion from acinar cells is blocked and digestive enzyme zymogens become colocalized with lysosomal hydrolases within intracellular vacuoles. Presumably, those vacuoles are the site of zymogen activation--a process which may be mediated by lysosomal hydrolases. The relationship between biliary tract stone passage and the onset of pancreatitis is complex but the evidence presented suggests that pancreatic duct obstruction and not bile reflux into the pancreatic duct is sufficient to trigger acute pancreatitis.