Changes in oxidative stress in children undergoing chemotherapy for acute lymphoblastic leukemia (ALL) have not been well documented. To determine whether the measurement of the DNA oxidized base 8-oxodeoxyguanosine (8-oxo-dG) may be a useful biomarker in this population, the authors conducted an observational study on 103 children with ALL. Blood samples were collected at diagnosis, during interim maintenance (IM), and during delayed intensification (DI). Blood mononuclear cell 8-oxo-dG, measured with an immunohistochemical method, decreased from diagnosis to IM (P = .01) and increased between IM and DI (P < .01). In a pilot study, bone marrow was also collected from 16 patients at diagnosis and after 28 days of treatment, but 8-oxo-dG remained the same. The relationship between plasma and dietary intake of antioxidants and the level of 8-oxo-dG was also explored. There was a direct relationship between the intake of vitamin E at diagnosis and bone marrow 8-oxo-dG (P = .03) and an inverse relationship between beta-carotene intake and blood 8-oxo-dG at IM (P = .03) and vitamin A in-take and blood 8-oxo-dG at DI (P = .003). Plasma vitamin C (P = .02) and total carotenoids (P = .01) were inversely related to blood 8-oxo-dG at IM. In contrast, higher plasma E/total lipid levels were associated with higher 8-oxo-dG at IM and DI (P < .01). At IM, patients with higher 8-oxo-dG had an increased risk of chemotherapy dose reduction (P = .04). In conclusion, the level of 8-oxo-dG in blood mononuclear cells decreases after the start of chemotherapy and increases during aggressive chemotherapy in children with ALL.