The involvement of lysosomes in the normal secretory process of the exocrine pancreas and in the onset of acute, hormone-induced pancreatitis was studied. The enzymatic activities of cathepsin B and .beta.-galactosidase were determined in the pancreas of rats that were stimulated by either maximal (0.25 .mu.g/kg/h) or supramaximal (5 .mu.g/kg/h) concentrations of cerulein. Maximal stimulation led to a moderate increase in cathepsin B activity and the ultrastructural appearance of multivesicular bodies. Supramaximal stimulation resulted in formation of large cytoplasmic vacuoles and progressive destruction of acinar cells which was paralleled by a marked increase of lysosomal enzyme activity.