The substitution effect on hydrogen bond energy of the Watson-Crick type base pair between uracil and chemically modified adenine derivatives was evaluated by ab initio molecular orbital theory. Predicted hydrogen bond energies were compared with experimental binding constants in some cases, and the calculated hydrogen bond energies correlated well with the experimental binding constants. Thus, ab initio calculation is an effective method to estimate the stability of the base pair between chemically modified nucleic acid bases. In contrast to the substitution effect in uracil on hydrogen bond energy, no remarkable trend was observed in the relation between the substituent in adenine derivatives and the hydrogen bond energies. The adenine derivatives, which have a nitro group on the 8-position or an amino group on the 2-position, can form the most stable hydrogen bonds with uracil.