The ribonuclease A transphosphorylation mechanism is studied using ab initio quantum chemical methods, incorporating for the first time detailed all-electron components which mimic important amino acid residues within the enzyme active site. The 2-hydroxyethyl methylphosphate monoanion is chosen as a model substrate, methyleneimines (CH2NH) are used in place of the imidazole rings for His-12 and His-119, and methylamine (CH3NH2) is used in place of Lys-41. Each pseudoresidue is held fixed in its appropriate relative position found crystallographically. Within this model, structures and relative energetics for the stationary points along the transphosphorylation reaction pathway are determined at the RHF level using a 3-21G+* basis set, The data reveal several low-barrier proton transfer steps between the substrate and the active site residues which allow transphosphorylation to occur with modest activation, consistent with experimental results for the actual enzyme. Two distinct aspects of the active site are identified : a general acid to help protonate the substrate and an acid/base pair which cooperatively facilitates proton transfer as transphosphorylation takes place.