This article is available online at http://www.jlr.org behavioral and lifestyle factors over the life course. Infl ammation is a major component of atherosclerosis and an important factor in the early phase of arteriosclerosis ( 1 ). C-reactive protein (CRP), an acute phase reactant and a biomarker of systemic infl ammation, is associated with adverse cardiovascular outcomes ( 2 ). There is also strong evidence that CRP is an independent predictor of increased cardiovascular risk ( 3 ), supporting a role for CRP in CVD risk prediction ( 4, 5 ). Smoking exposure, adiposity, and the use of oral contraceptives (OCs) have been shown to be related to higher CRP levels in studies in adults ( 6-9 ). Raised CRP levels later in life refl ect lifetime exposure to smoking as well as adiposity levels ( 10 ). Further, sex differences in the association between CRP levels and other risk factors have been described. For example, leptin was shown to be associated with higher CRP levels in women but not in men ( 11 ), while adiponectin was shown to be inversely associated with CRP in females ( 12 ). Elevated CRP levels in smokers may contribute to the adverse effect of smoking on CVD risk; hence, both smoking and CRP have been incorporated in the Reynolds Risk Score for women in CVD risk assessment ( 13 ), as recommended by the American Heart Association ( 14 ). Moreover, sex differences have been reported in the relationship between smoking and subclinical infl ammation in adults ( 15 ).Studies in adults have documented that smoking may reduce the effi cacy of OCs ( 16 ), and may adversely affect menstrual cycle control in OC users ( 17 ). Estrogen levels were shown to be lower in smokers, compared with nonsmokers ( 18 ). The cause of the anti-estrogenic effects of smoking may be an increase in the catabolism of estrogen ( 19 ). To our knowledge, the potential interaction between smoking and OC use in relating to CRP levels in adolescence has not been studied. Atherosclerosis, the primary underlying pathological process that eventually leads to ischemic heart disease, begins early in life, and is infl uenced by potentially modifi able Abbreviations: CRP, C-reactive protein; hs-CRP, high-sensitivity C-reactive protein; OC, oral contraceptive; PWC 170 , physical working capacity at a heart rate of 170 beats per minute.