An extensive analysis of the free energy profile for the reaction of the hydroxide ion with ethyl acetate in both aqueous and dimethyl sulfoxide (DMSO) solutions has been carried out using ab initio calculations and including the solvent effect by the polarizable continuum model. Different reaction pathways were investigated, such as the usual B(AC)2 mechanism, the carbanion mechanism, the elimination mechanism, and the S(N)2 mechanism. Our calculation agrees with the view that in aqueous and DMSO solution basic hydrolysis occurs by the B(AC)2 mechanism. In water, the predicted activation free energy value is 17.6 kcal mol(-1), which is in very good agreement with the experimental value of 18.8 kcal mol(-1). Using a new parametrization of the polarizable continuum model adequate to describe anions and neutral species in DMSO, the present study predicts a rate enhancement by a factor of 435 in the reaction when going from water (protic solvent) to DMSO (dipolar aprotic solvent). In this solvent, the activation free energy is predicted to drop to 14.0 kcal mol(-1). Furthermore, our results point out that the elimination mechanism is only 6.0 kcal mol(-1) (DeltaG(Sol)(double dagger) = 20.0 kcal mol(-1)) less favorable than the B(AC)2 mechanism in DMSO solution, and 8.4 kcal mol(-1) less favorable in water. The S(N)2 and the carbanion mechanisms have barriers above 30 kcal mol(-1) in water and DMSO and are thus highly unfavorable. These results suggest the elimination mechanism can become the dominant pathway in the basic hydrolysis of sterically crowded esters at the carbonyl center.