Mesotrypsin, an inhibitor-resistant human trypsin isoform, does not acti-vate or degrade pancreatic protease zymogens at a significant rate. These observations led to the proposal that mesotrypsin is a defective digestive protease on protein substrates. Surprisingly, the studies reported here with a1 -antitrypsin (a1AT) revealed that, even though mesotrypsin was com-