The hydrolysis of ethyl benzoate in acidic condition was theoretically studied for models with two (2W) or three water (3WA) molecules at the B3LYP/6-311++G(d, p) levels of theory. Activation free energy of solvation in aqueous solution (Delta G(cal)(+)) was calculated using the QM/MC/FEP method. The value of the 2W model in aqueous solution was calculated to be smaller by more than 5.0 kcal mol(-1) than the observed value (26.0 kcal mol(-1) at 298 K). The position of the third water molecule in the 3WA model plays an essential role in producing the Delta G(cal)(+) value (26.4 kcal mol(-1)) consistent with the experimental value. (C) 2012 Elsevier B.V. All rights reserved.