['Little is known about the association of leisure-time physical activity (LTPA) and cardiorespiratory fitness with development of the metabolic syndrome, which predisposes diseases such as diabetes and atherosclerosis. We studied the associations of LTPA and cardiorespiratory fitness with development of the metabolic syndrome (World Health Organization [WHO] and the National Cholesterol Education Program [NCEP] definitions).', 'LTPA over the previous 12 months, VO(2max) (ml. kg(-1). min(-1)), and cardiovascular and metabolic risk factors were assessed in a population-based cohort of 612 middle-aged men without the metabolic syndrome.', 'At the 4-year follow-up, 107 men had metabolic syndrome (WHO definition). Men engaging in >3 h/week of moderate or vigorous LTPA were half as likely as sedentary men to have the metabolic syndrome after adjustment for major confounders (age, BMI, smoking, alcohol, and socioeconomic status) or potentially mediating factors (insulin, glucose, lipids, and blood pressure), especially in high-risk men. Vigorous LTPA had an even stronger inverse association, particularly in unfit men. Men in the upper third of VO(2max) were 75% less likely than unfit men to develop the metabolic syndrome, even after adjustment for major confounders. Adjustment for possible mediating factors attenuated the association. Associations of LTPA and VO(2max) with development of the metabolic syndrome, as defined by the NCEP, were qualitatively similar.'] Do low levels of leisure-time physical activity and cardiorespiratory fitness predict development of the metabolic syndrome?