Quantitative structure-activity relationships (QSAR) have been formulated for the interactions of a variety of ligands with chymotrypsin. The parameters Km, k2, k3, kcat, and Ki are found to be strongly dependent on molar refractivity as well as steric and electronic character of the substituents in structures of the type R2CH(COOR3)NHCOR1 where R may be H. A model for binding of D and L esters is presented which gives a consistent view of the binding step, acylation, and deacylation. The model suggests new avenue for exploration.