The use of phosphorus compounds as tetrahedral transition state analogs will be evaluated as a strategy for designing enzyme inhibitors and, ultimately, rational drug design. Phosphorus compounds which mimic the tetrahedral intermediates in the reactions catalyzed by the nucleoside deaminases, aspartate transcarbamylase, the zinc-containing and serine peptidases, and the beta-lactamases will be synthesized and tested as inhibitors of these enzymes. These compounds may prove valuable in mechanistic studies, in potentiating clinically important antineoplastic and antimicrobial drugs, and as pharmacological agents in their own right.