Objective-This study examined the association between cardiorespiratory fitness and C-reactive protein (CRP), with adjustment for weight and within weight categories. Methods and Results-We calculated median and adjusted geometric mean CRP levels, percentages of individuals with an elevated CRP (Ն2.00 mg/L), and odds ratios of elevated CRP across 5 levels of cardiorespiratory fitness for 722 men. CRP values were adjusted for age, body mass index, vitamin use, statin medication use, aspirin use, the presence of inflammatory disease, cardiovascular disease, and diabetes, and smoking habit. We found an inverse association of CRP across fitness levels (P for trendϽ0.001), with the highest adjusted CRP value in the lowest fitness quintile ( Key Words: C-reactive protein Ⅲ cardiorespiratory fitness Ⅲ men E levated plasma C-reactive protein (CRP) levels have been prospectively associated with increased risk of cardiovascular disease (CVD) in apparently healthy individuals. [1][2][3][4] There is an abundance of reports on the positive association between weight and CRP, and investigators have also shown that reduction in weight produces a reduction in CRP concentrations. [5][6][7][8][9][10][11] We have reported previously that fitness has beneficial effects on mortality and CVD risk factors that are independent of weight and evident within weight classifications. [12][13][14][15][16] Thus, when the relationship between weight and CVD risk factors or clinical outcomes is assessed, it is important to account for exercise habits or fitness level.There are only a few available studies examining the effect of regular exercise or exercise training on resting levels of CRP. 10,17,18 Geffken et al 17 found the amount of regular physical activity to be inversely related to CRP in a healthy elderly population, and Rohde et al 18 reported that healthy men who exercise Ͼ1 time a week had lower mean CRP than men who did not exercise at least once a week. Mattusch et al 19 found that 9 months of marathon training resulted in a 31% decrease in CRP (nϭ12), and Smith et al 20 reported a nonsignificant (Pϭ0.12) decrease in CRP (Ϫ35%) after 6 months of exercise training in individuals (nϭ43) at high risk for ischemic heart disease. Although these studies provide evidence that regular exercise may reduce CRP values, each lacks either generalizability, adjustment for weight, a reliable measure of regular physical activity, or an adequate number of participants.Cardiorespiratory fitness is an objective laboratory measurement that reduces the misclassification bias that often results from self-reports of physical activity. Although cardiorespiratory fitness has a genetic component, it is primarily determined by habitual physical activity. 21,22 To our knowledge, there are no available reports on the association of cardiorespiratory fitness and CRP. The purpose of the present study was to examine the association between cardiorespiratory fitness and CRP, with adjustment for weight and also within weight categories. Understanding the relationsh...