We present an application of the recently proposed coupled reference interation site model (RISM)/molecular dynamics (MD) solvation free-energy method (Freedman, H.; Truong, T. N. Chem. Phys. Lett. 2003, 381, 362; J. Chem. Phys. 2004, 121, 2187) to study the hydration effect upon the tautomeric equilibria of 2-hydroxypyridine and 2-oxopyridine and of cytosine in water. In this methodology, simulation trajectories of solvated systems are computed and averaged to determine radial distribution functions, which are then inserted into a RISM expression for the solvation free energy. The computed differences in free energy of hydration for the two tautomerizations agree well with the experimental data as well as results from previous free-energy simulations. This is particularly encouraging since the coupled RISM/MD method requires a single MD simulation as compared to the more complicated and computationally demanding free-energy simulation methods.