This inhibitory fragment, released from native ITI after limited proteolysis with trypsin, contains two homologous domains. Whereas the second domain is a strong inhibitor of trypsin, the first domain interacts weakly with PMN-granulocytic elastase and not at all with pancreatic elastase. The amino acid at position p2' (17) appears to determine the specificity of the inhibition of domain I. Inhibitors with methionine in this position interact weakly with chymotrypsin and elastase; those with leucine interact strongly.