Extreme exercise increases oxygen uptake with a potential for increased formation of reactive oxygen species. Damage to biomolecules may occur if such an increase exceeds the protective capacity of antioxidant defence mechanisms. Vigorous exercise amounting to approximately 10 h a day for 30 days increased the rate of oxidative DNA modification by 33% (95% confidence limits, 3-67%; P < 0.02) in 20 men owing to the urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an oxidatively modified deoxynucleoside originating from nuclear DNA repair, oxidation of the nucleotide pool from mitochondrial DNA and/or from cell turnover. Oxidative stress to DNA points to a risk for the development of cancer and premature ageing from extreme exercise.