The substituent effect on geometries, energies, frequencies and charge distributions of the various DNA base pair derivatives was evaluated using density functional theory at B3LYP/6-31G* level. The results indicate that the fluorine-substituted cytosine has great influence over the stabilization energy of the various C:G derivatives while the nitro-substituted thymine affects the stabilization energies most deeply among all the A:T derivatives. The N-H stretching vibrational frequency is red shifted and the shift is almost linear correlated with the N-H bond length elongation. There is no direct relationship between the charge distribution and the stabilization energy. (C) 2003 Elsevier Science B.V. All rights reserved.