Phosphate monoester hydrolysis is studied theoretically with particular focus on solvent effects on the reaction mechanism. Free energy profiles for methyl monophosphate and triphosphate anions are calculated at the DFT/COSMO level by determining the reaction path with a chain-of-replicas method. The result suggests that in low dielectric environments, the stepwise mechanism involving prior metaphosphate dissociation is preferred over concerted one that involves a penta-coordinated transition state. It is discussed that the above preference for stepwise mechanism may be relevant for a dramatic increase in phosphate hydrolysis rate observed in low dielectric media. (C) 2010 Elsevier B.V. All rights reserved.