Carboxyl ester lipase was purified from human pancreatic juice. Antisera were raised in rabbits and the monospecificity of the antibody was verified by immunoblotting. The enzyme was present in zymogen granules of acinar cells, in occasional duct cells, and in secretory material in normal pancreas in immunohistochemistry. Also, occasional cells in the epithelium of small intestinal villi but not the granules of Paneth cells, were stained. Decreased and evenly dispersed staining was observed in necrotic acinar cells in acute pancreatitis, whereas the reaction was intensive in plugs in acinar lumina. Interstitial staining was seen around necrotic pancreatic lobules and in areas of fat necrosis. This staining pattern is similar to that obtained with antisera against other lipolytic pancreatic proteins, but differed from that with antisera against trypsin and pancreatic secretory trypsin inhibitor. We conclude that carboxyl ester lipase behaves similarly to the other lipolytic enzymes during acute pancreatitis and that interstitial localization of secretory lipolytic enzymes is characteristic of the necrotizing inflammatory process in pancreas.