The energetic provisions for Lowdin’s DNA mutational mechanism (Lowdin, P. O. Rev. Mod. Phys. 1963, 35, 724) of the formation of substitution DNA mutations were investigated for the guanine cytosine Watson-Crick base pair. The structures studied involve the canonical base pair (GC1), rare base-pair tautomers that are formed from GC1 by the antiparallel simultaneous transfer of two protons in hydrogen bonds, and ion-pair structures that are formed by the transfer of a single proton. The geometries of these complexes were optimized by nb initio Hartree-Fock (HF) calculations using the 6-31G* basis set. At the same level, harmonic vibrational frequencies were determined. Nonplanar geometries featuring considerable propeller-twist angles and a pyramidal guanine amino group were found for base pairs involving the guanine anion and 6-hydroxyguanine. The relative stabilities and dissociation energies of the base pairs were determined at the higher MP2/6-31G**//HF/6-31G* level of theory. These methods were also used to locate transition states on the potential energy surface of the guanine cytosine base pair. Starting from the geometries of two different transition states lying close to the ion-pair G(-)C(+) minimum, the intrinsic reaction coordinate for the proton transfer from the canonical to the 6-hydroxyguanine . 4-iminocytosine tautomer (GC2) was evaluated. We concluded that, in contrast to the adenine thymine base pair (for which Lowdin’s mutational mechanism is not supported by the present theoretical data), the GC1-->GC2 tautomeric transition is likely to occur in 1 in 10(6)-10(9) guanine cytosine base pairs. This frequency is significant from the point of view of the fidelity of DNA replication.