Alpha 1-antichymotrypsin (alpha 1-AC) is a protein that inhibits chymotrypsinlike proteinases, such as leukocyte cathepsin G. It also inhibits cytotoxic "killer" cell activity in vitro and may therefore be important for the control of immunologic and inflammatory processes in the lung. Alpha 1-AC is present in lung secretions at high concentrations, suggesting local production within the lung. We investigated the possibility that alveolar macrophages may be capable of synthesizing and secreting alpha 1-AC. Human alveolar macrophages were cultured in the presence of L-75Se selenomethionine, and the culture supernatants were examined by immunoelectrophoresis followed by autoradiography. The results showed that the radio-amino acid was incorporated into alpha 1-AC, suggesting de novo synthesis of the protein. Cycloheximide inhibited incorporation of the label. Immunohistochemical staining of human lung tissue for alpha 1-AC showed the protein to be present within alveolar macrophages.