Hartree-Fock, Moller-Plesset, and DFT calculations have been carried out using the 6-31++G** basis set to study the effect of microsolvation on the strength of a typical low-barrier hydrogen bond. In the gas phase, the hydrogen bond formed between a formic acid molecule and a formate anion is approximately 25 kcal/mol, with a calculated energy barrier for proton transfer from the formic acid to the formate anion which is lower than the zero point vibrational energy resonant in the system. When both the formic acid and formate anion are microsolvated, by one water molecule each, the resulting hydrogen bond is actually increased in strength slightly. When the microsolvation is asymmetrical, however, so as to cause a mismatch in the pK(a) values of the hydrogen bond donor and hydrogen bond acceptor, the resulting H-bond is weakened by approximately 4 kcal/mol. These results suggest that small amounts of interstitial water in enzyme active sites may not preclude the existence or importance of low-barrier hydrogen bonds in such biological catalysts.