We report our detailed electronic MCD, CD, and optical spectroscopic measurements and analysis of the porphyrin Soret (B0) region of four‐coordinate 5,10,15,20‐tetrakis(4‐N‐methylpyridyl)porphyrinatopalladium(II), PdP(4), and its bound states with B‐DNA duplexes poly(A‐T)2, poly(G‐C)2, and calf thymus DNA (CT DNA). For system PdP(4)/poly(A‐T)2 it was possible to conclude that the porphyrin is bound edge‐on in the major groove, specifically at the 5′AT3′ site. For this orientation the porphyrin's electric dipole transition moments (edtm), μx (most perturbed direction) and μy (least perturbed direction), have tilt angles α ∼ 90° and ∼ 45°, respectively, relative to the helix axis. It was further concluded from the small shifts of B0 optical and MCD band intensities and wavelengths and from the net MCD (+) A‐term sign retention upon binding that the porphyrin's frontier pπ MOs (1a1u 3a2u 4eg) are only weakly perturbed by the heterocyclic bases of poly(A‐T)2, and therefore that the LUMO (4eg) splitting is less than the |1a1u−3a2u| energy separation, ΔHOMO, that is, ΔLUMO < ΔHOMO for the bound state in PdP(4)/poly(A‐T)2. For intercalation systems PdP(4)/poly(G‐C)2 and /CT DNA, with PdP(4) centered in the intercalation “pocket” and having two of its 4‐N‐methylpyridyls extending into each of the major and minor grooves, the edtms μx and μy were determined to be oriented perpendicular (γ ∼ 0°) and parallel (γ ∼ 90°) to the hydrogen bonds of the base pairs, respectively. Intercalation is characterized by a much stronger binding interaction, viz., the B0 optical band and net MCD extrema wavelength shifts are relatively large, and the net MCD (+) A‐term of PdP(4) is substantially quenched as it becomes the (−) pseudo‐A‐term of intercalated PdP(4)/poly(G‐C)2. This A‐term sign reversal informs that the porphyrin MOs are so strongly perturbed by the GC base pairs that ΔLUMO > ΔHOMO, which gives rise to a (−) pseudo‐A‐term. Also, the findings demonstrate (1) the potential of PdP(4) as a sensitive, discriminating analytical probe of DNA sequences and (2) the diagnostic capability of the composite of five spectra [net MCD, CD, and optical of free and bound PdP(4)] in differentiating the site and sequence selectivity and preferred binding mode of this porphyrin. © 1999 John Wiley & Sons, Inc. Biospectroscopy 5: 179–188, 1999