The spectral properties of meso-tetrakis(N-methylpyridinium-4-yl)porphyrin (TMPyP) complexed with poly[d(I-C)(2)] were compared with that bound to poly[d(G-C)(2)] and poly[d(A-T)(2)]. At low TMPyP/DNA base ratios, the TMPyP-poly[d(I-C)(2)] complex exhibits a similar NaCl dependent absorption and circular dichroism spectrum to that of the TMPyP-poly[d(A-T)(2)] Complex. The negative CD band in the Soret absorption region of these complexes disappears as the NaCl concentration reaches around 10 mM. At a NaCl concentration higher than 10 mM, the resulting positive CD band is pronounced. In contrast, the change in negative CD band of the TMPyP-poly[d(G-C)(2)] complex, which is believed to be intercalated, is small. The molecular plane of porphyrin in the TMPyP-poly[d(I-C)(2)] complex for both species associated with negative and positive CD is perpendicular relative to the polynucleotide helix axis. Therefore, it is indicative that TMPyP (partially) intercalates between the base pairs of poly[d(I-C)(2)] at a very low mixing ratio and NaCl concentration and exhibits an outside binding mode as the NaCl concentration increases. It then follows that the amine group of guanine that protrudes in to the minor groove either helps stabilize the intercalated TMPyP or serves to destabilize the minor groove binding.