Varying amounts of crystalline porcine pancreatic elastase were injected iv into puppies in order to study its effect in vivo on elastic tissue (21) and on serum elastase inhibitors. Serum inhibitors to pancreatic elastase and to trypsin, were determined in blood samples drawn at intervals after injection. The serum elastase inhibition level decreased 3-5 hr after elastase injection. The decrease was a function of the amount of enzyme injected and reached the highest levels at 80-200 mg elastase injected. The decrease of elastase inhibitor titer with injected elastase suggests a dissociable enzyme-inhibitor complex (es). No parallelism was observed between serum inhibitor titers to elastase and to trypsin. The trypsin inhibitor titer dropped only exceptionally and did not follow at any time the kinetics of the elastase inhibitors. The elastase inhibitor titer returned to normal 24 hr after injection of 20-150 mg of enzyme but only partial recovery was observed in this interval with higher doses. The relatively low affinity of the serum inhibitors to elastase may explain the tissue lesions observed even at low doses of elastase injected (20 mg). The authors express their deep appreciation to Dr. Jean Cachera and Dr. Jacques Hinglais for making available for these animal studies the excellent facilities of the Laboratoire D'Etude de Technique Churgical, CNRS of Hopital Broussais, Paris. Appreciation is also expressed to M. Jean P. Gascard and Mile. Jackeline Hoerter for their fine technical assistance.