Irradiation of the red-light absorbing dye, methylene blue (MB), in the presence of the metal complex, cis-Rh(phen)₂Cl₂ (BISPHEN), leads to irreversible photobinding of both reagents to DNA. Evidence from absorption and emission spectroscopy indicates that the dye is strongly complexed to the DNA at the concentrations used in the experiments and that this complex is unaffected by the presence of BISPHEN. The level of covalent binding is proportional to the absorbed light dose, with the quantum efficiency for covalent binding of BISPHEN to the DNA with 633 nm light equal to 3.5 × 10⁻⁴. Electrospray ionization mass spectrum of a mixture of DNA fragments created by enzymatic degradation of DNA isolated following irradiation indicates that purine adducts are formed with both BISPHEN and the dye. In addition, UV–Vis and high-performance liquid chromatography analyses of the irradiated MB/BISPHEN/DNA mixture and isolated adducts show extensive conversion of the dye and metal complex to the corresponding N-demethylated and aquated derivatives, respectively. Triplet quenchers for MB, for example oxygen and benzoquinone, inhibit both the photoconjugation and the photochemistry of BISPHEN. A mechanism for the synergistic interaction is proposed that involves photoconjugation of both partners to the DNA following oxidation and reduction via electron transfer between ¹MB^*/DNA and ³MB^*/BISPHEN.