Organic compounds which can selectively but irreversibly react with amino acid residues near the active center of alpha-chymotrypsin (and other serine proteases), serum albumins and other proteins are being synthesized. In favorable cases the kinetics of the inactivation process are followed. These compounds contain fluorine substituents and a few will be enriched in carbon-13. High resolution and pulsed n.m.r. investigations of the resulting protein derivatives provide information about the molecular environment around the active site and should indicate how that environment changes in the presence of small organic molecules or when solution variables such as pH and temperature are changed. It is hoped that this work will eventually lead to new approaches to the design of active-site directed chemotherapeutic agents.