In order to provide a body of basic information on transition states and mechanistic features of group-transfer reactions, particularly acyl-transfer reactions, as they occur in non-enzymic and enzymic systems of medical importance, experimental measurements (largely of kinetic isotope effects) will be employed in concert with model calculations. Systems for study include nucleophilic and electrophilic reactions of esters and amides and the action of peptidases, esterases and amidases as well as prosesses of association and the transfer of phosphorus and sulfur groups. The resulting data and generalizations are expected to contribute to the development of highly potent and specific drugs through the transition-state analog, suicide-inhibitor and pro-drug approaches, and perhaps through new approaches based on the syncatalytic and paracatalytic inhibitor concepts.