An unadecapeptide, obtained by papain digestion of denatured human alpha-1-proteinase inhibitor (alpha-1-PI), has been isolated and sequenced. The structure of this fragment overlaps with the NH2-terminal sequence of modified inhibitor (alpha-1-PI) prepared from dissociated complexes of alpha-1-PI with trypsin, chymotrypsin, and elastase. Furthermore, structural homology with the reactive centers of proteinase inhibitors from other sources is readily detectable. Methionine has been found to occupy the apparent P1 position in alpha-1-PI and the potential inactivation of the inhibitor by oxidation of this critical residue may be important in obtaining a biochemical link with the development of lung disease.