Objective-This study was undertaken to evaluate to what extent C-reactive protein (CRP) can be reduced by exercise by examining its circulating concentrations in male ultramarathon runners and to determine if low leptin as a robust circulating marker of fat mass could account for low CRP in such men. Methods and Results-Sixty-seven male ultramarathon runners and 63 sedentary male controls of similar age and body mass index were recruited. CRP and leptin were measured by ELISA and radioimmunoassay, respectively. Median CRP concentration in lean (body mass index Ͻ25 kg/m 2 ) marathon runners was less than half control median (0. Circulating leptin levels were also substantially lower in lean (45% less) and nonlean (63% less, both PϽ0.0001) ultramarathon runners. However, interleukin-6 levels were not different. Furthermore, leptin adjustment only minimally attenuated the case-control difference in CRP, suggesting that mechanisms other than fat mass reduction contribute to low concentrations of CRP in marathon runners. Conclusions-This