The hydrolysis of the phosphate diester bis(2-(1-methyl-1H-imidazolyl)phenyl) phosphate BMIPP was evaluated as an intramolecular model for the ribonuclease A mechanism. Kinetic and thermodynamic data, isotope effects and ESI-MS and ESI-MS/MS analysis support the proposed intramolecular general acid-base catalysis by the imidazole groups.