This paper develops and examines a hybrid ab initio quantum mechanical/molecular mechanics method for the calculation of activation free energies of chemical reactions in solution and in proteins. This method uses molecular mechanics force fields to simulate the solvent and an ab initio technique that incorporates the potential from the solvent in its Hamiltonian to simulate the solute. The empirical valence bond (EVE) method is used as a reference potential for the ab initio free energy calculation, thus overcoming the problems encountered by direct attempts to use molecular orbital methods in calculations of activation free energies. The paper examines in detail the shortcomings of such alternative methods, demonstrating that they are likely to miss the contribution of the solvent coordinates to the activation barrier. It also explains how and why this problem is avoided with the EVE mapping procedure. The utility of our method is illustrated by calculating the activation free energy for proton transfer from a water molecule to a hydroxide ion in both aqueous and nonpolar solutions. This paper also demonstrates that the EVE Hamiltonian can be refined easily by fitting the EVE parameters to the charges and energies resulting from ab initio gas phase calculations; this technique may offer the optimal way to transfer the results of ab initio gas phase calculations to solution or a protein, as well as the most effective way of evaluating ab initio activation barriers in aqueous media.