An immunohistochemical study was performed to localize two distinct Ca2+-proteases (low-Ca2+-requiring calpain I and high-Ca2+-requiring calpain II) and their specific inhibitor (calpastatin) in human pancreas using the respective monospecific antibodies. Strongly positive staining by anti-calpain I antibody was found in pancreatic islets, specifically in B-cells, whereas the exocrine pancreatic tissue showed essentially no positive immunostaining. No such specific staining was found with anti-calpain II antibodies or anti-calpastatin antibodies. The results suggest that the Ca2+-dependent proteolysis in B-cells can be triggered by a small rise of the intracellular Ca2+ concentration without serious interference by the endogenous inhibitor.