The substitution effect on hydrogen bond energy of the Watson-Crick type base pair between 9-methylguanine and chemically modified 1-methylcytosine derivatives was evaluated by an ab initio molecular orbital theory. A remarkable tendency was observed, namely, that cytosine derivatives possessing an electron-donating group form a stable base pair with guanine. Nevertheless, neither the hydrogen bond distance nor the charge distribution was a valid index for the hydrogen bond status in Cx-G base pairing. An intramolecular hydrogen bond between the substituent and the exo-cyclic amino moiety also had an important role in the substitution effect of the base pair stability.