Many investigations on the reaction mechanism of carboxypeptidase A (CPA) have shown that the zinc ion and Glu 270 in the active site are important in the catalytic reaction with a peptide substrate. X-Ray crystallographic studies of native CPA showed that the zinc ion is coordinated to His 69, Glu 72, His 196, and one water molecule and that the Zn-coordinated water molecule forms a hydrogen bond with Glu 270. The zinc-water-Glu 270 system of native CPA was analyzed by the ab initio SCF-LCAO-MO method. Some ligands of zinc are included in the MO calculations as point fractional charges. The results show that the Zn-coordinated water molecule acts as a proton donor to Glu 270, and that the electrostatic effect of Zn2+ and its ligands and the electron delocalization between Zn2+ and the water play a significant role in lowering the barrier height of proton transfer. We consider that the carbonyl group of the substrate, without breaking the hydrogen bond between Glu 270 and the Zn-coordinated water molecule, points towards a fifth coordination site slightly away from Zn2+, and that the water molecule itself is modified by its connection to Glu 270 in a way that favors the reaction.