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LEE, I-M., and P. J. SKERRETT. Physical activity and all-cause mortality: what is the dose-response relation? Med. Sci. Sports Exerc., Vol. 33, No. 6, Suppl., 2001, pp. S459–S471. Purpose: The purpose of this review is to assess the dose-response relation between physical activity and all-cause mortality. We examined these parameters of physical activity dose: volume, intensity, duration, and frequency. We used a computer-assisted literature search to identify papers on this topic. After excluding papers examining only two levels of physical activity or fitness, papers investigating specific causes of mortality, reviews, and those not written in English, 44 papers satisfying all criteria were included in this review. There is clear evidence of an inverse linear dose-response relation between volume of physical activity and all-cause mortality rates in men and women, and in younger and older (≥60 yr) persons. Minimal adherence to current physical activity guidelines, which yield an energy expenditure of about 1000 kcal·wk-1 (4200 kJ·wk-1), is associated with a significant 20-30% reduction in risk of all-cause mortality. Further reductions in risk are observed at higher volumes of energy expenditure. It is unclear whether a volume of <1000 kcal·wk-1 also may be associated with lower risk; there are some data supporting this. Due to limited data, it is also unclear whether vigorous-intensity activity confers additional benefit beyond its contribution to volume of physical activity when compared with moderate-intensity activity. No data are available on duration and frequency of physical activity in relation to all-cause mortality rates after controlling for volume of physical activity. All studies in this review are observational studies, so conclusions are based on Evidence Category C. There is an inverse linear dose-response relation between volume of physical activity and all-cause mortality. Further research is needed to clarify the contributions of its components—intensity, duration, and frequency—to decreased all-cause mortality rates.