The mechanism of alkylation at the exocyclic nitrogen of guanine in G.C base pairs has been studied using density functional theory at the B3LYP/D95** level. Protonation of the amino group was used asa model for this reaction. The calculations indicate that the reaction is facilitated by a temporary transfer of the H-bonding hydrogen from the guanine amino position to the cytosine oxygen within the H-bond. Thus, the cytosine "loans" its basicity to the guanine within the H-bonded base pair. These calculations explain the previously observed dependence of guanine alkylation upon the substituent at the 5-position of cytosine. The generality of catalysis via the temporary transfer of a H-bonding hydrogen within an H-bond, hydrogen-bond, acid/base catalysis (HBA/BC), is discussed. This form of catalysis might be important in biochemistry, materials science, and the solid state.