The benchmark nucleophilic substitution reaction Cl- + CH3Cl in water clusters of different sizes is studied using an empirical valence-bond model. The reaction activation-free energy, the variation in the system's electronic structure and other system properties are determined as a function of cluster size from 3 to 40 water molecules. The barrier height increases monotonically with the number of water molecules and reaches 90% of the value in bulk water with about 15 water molecules. The contribution of the water is analyzed utilizing a solvent coordinate and its coupling to the electronic state of the solute. The dynamical correction to the rate due to barrier re-crossing is small. (C) 2010 Elsevier B.V. All rights reserved.