Recent studies using experimental models of acute pancreatitis suggest that events blocking evoked secretion of digestive enzymes from acinar cells may play an important role in the pathogenesis of this disease. Under these conditions, digestive enzymes become co-localized with lysosomal hydrolases within large intracellular vacuoles, where activation of trypsin by the lysosomal enzyme cathepsin B could initiate the cascade activation of the other pancreatic zymogens. Development of acute pancreatitis might, therefore, be initiated by events occurring within acinar cells rather than in the ductal system or the interstitium of the gland.