A flash-quench method has been developed to probe oxidative damage to DNA. A photoexcited Ru(II) intercalator is quenched in DNA by a weakly bound, electron-transfer quencher to generate Ru(III), a powerful ground-state oxidant. Once generated, Delta-Ru(phen)(2)(dppz)(3+) bound to poly(dG-dC) rapidly oxidizes guanine within the DNA duplex. Transient absorption spectroscopy indicates rapid formation of the neutral guanine radical within the DNA duplex. Permanent damage resulting from the flash-quench experiment is monitored by gel electrophoresis of synthetic oligonucleotide duplexes. Oxidative damage, visualized by treatment with piperidine, occurs selectively at the 5’-G of 5’-GG-3’ sites and at the 5’- and central G of 5’-GGG-3’ triplets; enzymatic digestion in the absence of piperidine treatment shows formation of 8-oxo-2’-deoxyguanosine with Ru(NH3)(6)(3+) as quencher. The yield of base damage is, furthermore, modulated by the choice of electron-transfer quencher. Quantum yields for damage vary in the order Ru(NH3)(6)(3+) < methyl viologen(2+) < Co(NH3)(5)Cl2+ and correlate with the instability of the reduced quencher. The flash-quench method, combining spectroscopy and product analysis, offers a novel and tunable approach to explore electron transfer chemistry on double helical DNA.