The purpose of this study was to determine whether the Ni(II)-tetraglycine complex system (NiG 4) that is known to disproportionate H 2O 2 at pH ≥ 8 can catalyze oxidation of the guanine residues in 2′-deoxyguanosine (dG), calf thymus DNA, and calf thymus nucleohistone (NH) by H 2O 2 at physiological pH. Incubation of dG with H 2O 2 in the presence of NiG 4 at 37°C, produced two effects: (a) formation of 8-hydroxy-2′-deoxyguanosine (8-OH-dG) and (b) decomposition of dG to 2,6-diamino-4-hydroxy-5-formamidopyrimidine and several low molecular weight unidentified products. The magnitude of both effects depended on incubation time (1–48h), H 2O 2 concentration (7.5–40 mM), NiG 4 concentration (0.1 or 1 mM), and pH (6.0–8.0). The effects were not detected below pH 6 and above pH 8.0. For 0.1 mM NiG 4 and 7.5 mM H 2O 2, production of 8-OH-dG from dG (0.75 mM) during 24 h at 37°C was significantly lower than from NH (1 mg/ml) or DNA (0.5 mg/ml), indicating possible specific effects that might be related to the strength of interaction of NiG 4 with dG, NH, or DNA. The results indicate production of hydroxyl radical or other oxidizing species in the reaction of H 2O 2 with NiG 4 at pH 7–8. Reactions like this may be relevant to the mechanisms of Ni(II)-mediated oxidative damage, observed in vitro and in vivo, which may contribute to the toxic and carcinogenic effects of this metal.