The substitution effect on hydrogen-bond energy of the Watson-Crick type base pair formation between 1-methylcytosine and chemically modified 9-methylguanine derivatives was evaluated by an ab initio molecular orbital theory. Introduction of an electron-withdrawing group on the 8-position or on the exo-cyclic amino moiety enforced the hydrogen bond. Neither the charge distribution nor the separation between the hydrogen bonding sites is found to be directly correlated with the strength of the hydrogen bonds.