Alpha-1-antitrypsin was demonstrated both by immunofluorescence and immunoperoxidase techniques in the peripheral islet cells of 15 normal human pancreases, processed freshly and after embedding in paraffin. Normal human liver obtained from the same patients was negative. The immunohistochemical reactions were stronger in frozen sections than in paraffin material. However, immunoperoxidase staining on paraffin sections permitted a more precise localization of positive cells. The specificity of the immunohistochemical reactions was confirmed by applying various control tests including a absorption of the specific antisera with purified alpha-1-antitrypsin, inhibition and blocking tests. Further examination of pancreatic tissue for the presence of various immunoglobulins, alpha-1-lipoproteins, alpha-1-acid glycoproteins and ceruloplasmin were negative. These findings suggest that the pancreatic islets may be an extra source of alpha-1-antitrypsin.