Generation of reactive oxygen species from mitochondrial respiration has been proposed as an important determinant of longevity and cumulative cancer risk. Interspecies correlations and animal calorie restriction studies of metabolic rate and oxidative DNA damage support this notion. In the present study we have demonstrated a close association between oxidative DNA damage as assessed by the urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and oxygen consumption in 33 healthy premenopausal women (r = 0.64; p = 0.00007). In the 12 women who smoked, 8-oxodG excretion was increased by 35%, although oxygen consumption increased only 10% compared with the 21 non- smoking women. Apparently, the rate of oxidative DNA damage relates to mitochondrial respiration in humans and is aggravated by smoking.