Background Cigarette smoking is a well known risk factor for cardiovascular diseases [1]. Commonly accepted pathophysiological mechanisms underlying many cigarette smoking associated adverse health effects are inflammation [2,3], oxidative stress [2,4], platelet activation [5,6] and abnormal lipid metabolism [7,8]. Suitable biomarkers of potential harm (BOPH) have been identified for these four different pathophysiological pathways: white blood cell counts (WBC) for inflammation [3,9,10], urine 8-epi-prostaglandin F2α (EPI8) for oxidative stress [11-13], urine 11-dehydro-thromboxane B2 (DEH11) for platelet activation [11,13,14], and high-density lipoprotein cholesterol (HDL) for abnormal lipid metabolism [15]. The Total Exposure Study (TES) was a stratified, cross-sectional, multi-center study in 3585 adult smokers and 1077 nonsmokers, designed with the primary objective of estimating the exposure to cigarette smoke constituents in a population of U.S. adult cigarette smokers [16]. A secondary objective of the study was to investigate the relationship between cigarette smoke exposure and biomarkers of potential harm. The purpose of this study was to explore relationships between the variables in the TES and four biomarkers of potential harm and to capture those relationships in statistical models.