Exposure of mammalian cells to oxidative stress can result in DNA damage that adversely affects many cell processes. We used bulk electrolysis in an electrochemical system and capillary electrophoresis (CE) to control and measure the effect of oxidative stress on DNA. Calf thymus DNA and a fiuorescently labeled DNA sizing ladder were subjected to fixed oxidizing potentials using a reticulated vitreous carbon electrode (RVC) and their fragmentation was measured with the use of CE. The resulting electropherograms showed that the oxidative treatment resulted in DNA fragmentation. Poly adenosine (Poly A) 40mer and poly guanosine (Poly G) 40-mer oligonucleotides were exposed to a controlled oxidative environment at constant potential values E = 0.5 V, 1.0 V, 1.5 V, and 2 V (vs Ag/AgCl) for 1 hour in 0.1 mol/L potassium phosphate buffer pH 7.3. The treated DNA fragments were analyzed by CE. The areas of the CE peaks were measured and the percentage of DNA fragmentation was calculated. Only minor fragmentation was observed when oligonucleotides were exposed to E = 0.5 V, with strand scission starting at electrode potentials E > 1.0 V. The E = 2.0 V treatment resulted in approximately 50% fragmentation of Poly A, compared to approximately 15% for the Poly G. These results, using DNA as a test model, demonstrate that controlled-potential electrolysis can be used to produce desired levels of oxidative damage to biomaterials without the need to use oxidative chemicals, which are difficult to control and relate to thermodynamic models. 2013 The Electrochemical Society. All rights-reserved.