BACKGROUND: Clinical studies have shown that elevated serum concentrations of cell adhesion molecules such as inter-cellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), E-selectin (ESEL) and P-selectin (PSEL) may be independent risk factors for atherosclerosis and cardiovascular disease (CVD). Less is known of the relationship of these inflammatory markers with established CVD risk factors in healthy individuals, particularly women. OBJECTIVE: The aim of this study was to examine cross-sectional relationships between the concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1, sPSEL and sESEL) and smoking behaviour, body composition, blood pressure, serum lipids and physical activity in a large sample of healthy men and women, with special emphasis on interactions between smoking and other CVD risk factors. SUBJECTS: The analysis included 592 healthy white adults aged 18-82 years. RESULTS: There were no sex differences in the concentrations of sICAM-1, sVCAM-1 and sPSEL, but men had higher sESEL levels than women (p < 0.0001). Male and female smokers had higher sICAM-1 and sESEL levels than non-smokers and soluble cell adhesion molecules (CAMs) were correlated with the pack-years of cigarette smoking (r = 0.3-0.4, p < 0.0001, significant in women only). Significant independent associations were found between soluble CAMs and smoking, waist-hip ratio (WHR), blood pressure, high density lipoprotein cholesterol and total cholesterol. Furthermore, significant interaction effects were found in women, such that the relationship between CAMs and lipid concentrations and WHR were stronger in smokers than non-smokers. In conclusion, the concentration of soluble CAMs, particularly sICAM-1 and sESEL, reflect the level of established CVD risk factors in apparently healthy men and women, adding to the evidence that these factors contribute to CVD through their inflammatory effects on the vascular endothelium.