Abstract— The photobleaching of excited tris(2,2′‐bipyridyl)‐ruthenium(II), *Ru(bpy)32+, by peroxydis‐ulfate in the presence of DNA and a series of polynucleotides, mononucleosides (uridine, cytidine, adenosine, guanosine), and purine or pyrimidine bases was studied in deoxygenated aqueous solution at room temperature. A reaction scheme is proposed which is confirmed by data obtained from mixing experiments with Ru(III) and bleaching measurements of Ru(II) using either continuous visible light or a nanosecond laser pulse (353 nm). The primary photobleaching step is the formation of Ru(bpy)32+ and the SO4‐ radical anion. In the presence of nucleic acids the two oxidizing species are formed in close proximity to the strand, since we used conditions where the Ru(bpy) 32+ ion is bound to the strand. Concerning the secondary reactions two clear cases (and several more complex cases) can be distinguished. On addition of uracil to the Ru(bpy)32+/S2O82‐ system the quantum yield for photobleaching is not significantly changed (φrel⋍ 0.95), whereas it drops to virtually zero for guanosine‐containing substrates, including DNA. The former result is explained by a reaction of SO4‐ with uracil leading to theN–1 radical which oxidizes Ru(II) to Ru(IIl). In contrast, the guanine moiety reacts with Ru(III) converting it into Ru(II). Therefore, in the presence of S2O82‐ and a substrate carrying a guanine moiety, Ru(bpy32+ acts as a photocatalyst.