Alpha 1-antitrypsin is a plasma serine protease inhibitor originally used as a marker for tumors of histiocytic origin. Our casual finding of immunoreactive alpha 1-antitrypsin in one case of thyroid papillary carcinoma led us to investigate its presence in 10 thyroid papillary carcinomas by applying immunocytochemical and immunochemical techniques to tissue sections and Western blots of tissue homogenates prepared from neoplastic tissue and from uninvolved normal areas in the vicinity of each tumor. The immunocytochemical study was performed in both thyroid tissue and metastatic regional lymph nodes. This analysis revealed immunoreactivity for alpha 1-antitrypsin in nine of the 10 cases studied. Immunoreactivity was intense in some of the cells forming the papillar and follicular structures. These cells were intermingled with completely unstained tumoral cells. In contrast to neoplastic tissue, the normal thyroid tissue present in the vicinity of each tumor showed no staining for alpha 1-antitrypsin. The electrophoretic analysis performed on homogenates prepared from both tumoral and normal thyroid tissue revealed a drastic reduction in the band corresponding to thyroglobulin in the tumoral tissue compared with normal thyroid extracts, where it represented the major protein. Western blotting and immunoprinting with a polyclonal alpha 1-antitrypsin antibody confirmed the results obtained with immunocytochemistry about the presence of this protease inhibitor in neoplastic thyroid tissue. Immunoprinting with the anti-alpha 1-antitrypsin antibody revealed an intense immunoreactive band of 53 kDa in the extracts prepared from tumoral tissue. This band had exactly the same apparent molecular mass previously described by others for alpha 1-antitrypsin purified from plasma and was identical to the molecular mass of the purified commercial standard employed.