This paper describes the synthesis and characterization of a new series of sterically nondemanding, dicationic porphyins that exhibit novel DNA-binding interactions. Cationic porphyrins continue to be the focus of a great deal of effort because of the promise they have for use in photodynamic, antiviral, and anticancer therapies. The systems explored here include 5,15-di(N-methylpyridinium-4-yl)porphyrin (H(2)D4), 5,15-di(N-methyipyridinium-3-yl)porphyrin (H(2)D3), and 5,15-di(N-methylpyridinium-2-yl)porphyrin (H(2)D2), as well as Zn(D4) and Zn(D3), the zinc(II)-containing derivatives of H(2)D4 and H(2)D3, respectively. Viscometry studies, in conjunction with various spectroscopic techniques, reveal the nature of the adducts formed with DNA. Irrespective of the base composition, H(2)D4 and H(2)D3 bind to DNA by intercalation. The zinc derivatives Zn(D4) and Zn(D3) are also intercalators; however, the binding constants are smaller because uptake requires the loss of an axial ligand. The decisive roles that steric factors and structural rigidity play in shaping the adducts with DNA become clear. Sequences that contain mainly adenine-thymine base pairs easily depart from the canonical B-form DNA structure and generally accommodate bulky porphyrins in external binding sites. However, with the H(2)D3 and H(2)D4 systems, the steric requirements are so minimal that intercalation becomes the preferred mode of binding, even in [poly(dA-dT)](2). The intercalated form of the H(2)D2 isomer is less stable, probably because of frontal strain associated with the (N-methyl) pyridinium-2-yl groups. A qualitative energy-level diagram is useful for assessing the forces that influence binding and could guide the design of new porphyrin ligands.