The inhibition of chymotrypsin activity by pig, dog, human and rat blood plasma was studied. N-Benzoyl-L-tyrosyl-p-amino-benzoate (PABA-peptide) was used as the substrate. Crystalline bovine chymotrypsin as well as activated lyophilized human, pig, rat and chicken pancreatic secretions were used as enzyme sources. Certain species differences were noted. Swine plasma had no effect on bovine or human chymotrypsin while it inhibited that of the chicken by 67%. Dog plasma was a potent inhibitor of chymotrypsin activity from all sources tested. An acute pancreatitis model using the rat was also developed in which pancreatic juice flow was blocked without interference with biliary flow. After 24 h, these animals had increased plasma amylase activity, decreased plasma protease inhibitor and decreased hematocrit. By 72 h, amylase, trypsin inhibitor and hematocrit had nearly recovered while chymotrypsin inhibitor had actually increased above control levels. In rats subjected to hepatectomy or to hepatectomy plus pancreatic blockage, plasma protease inhibitor was even more severely depressed and remained so.