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KOHL, H. W., III. Physical activity and cardiovascular disease: evidence for a dose response. Med. Sci. Sports Exerc., Vol. 33, No. 6, Suppl., 2001, pp. S472–S483. To summarize and synthesize existing literature providing evidence of a dose-response relation between physical activity and cardiovascular disease endpoints. MEDLINE search of indexed English-language literature through August 2000. Findings supplemented by existing consensus documents and other published literature. Only studies with greater than two physical activity exposure categories were included, and studies not focusing on the clinical manifestation of the outcome (incidence or mortality) were excluded. Existing studies were classified by outcome used: all cardiovascular disease (CVD), coronary (ischemic) heart disease (CHD), and stroke. The vast majority of the literature in this area has relied on prospective observational studies and has been conducted in European men or populations of men of primarily European descent. Follow-up intervals ranged from 3 to 26 yr, and most studies related a single initial measure of physical activity to the outcome of interest, sometimes many years in the future. No randomized trials of physical activity and cardiovascular disease as a clinical outcome exist. Taken together, the available evidence indicates that cardiovascular disease incidence and mortality, and specifically ischemic heart disease, are causally related to physical activity in an inverse, dose-response fashion. These findings have been demonstrated in a variety of populations and using a variety of physical activity assessment methods. Contrarily, equivocal evidence for stroke incidence and mortality prohibits a similar conclusion. No strong evidence for dose-response relation between physical activity and stroke as a CVD outcome is available. Physical inactivity is prominent in the causal constellation for factors predisposing to cardiovascular disease, particularly ischemic heart disease. Methodologic advances in physical activity assessment; additional studies on changes in the antecedent variable, physical activity, as it relates to the outcome; and more studies among women and ethnically diverse populations are needed to clarify these relations.