Soluble CD14 (sCD14), an effective mediator for the activation of monocytes by bacterial endotoxin is involved in the release of substances able to modify the characteristics of the arterial wall. The aim of this study was to investigate, in humans, the relationship of sCD14 with aortic stiffness and to analyse the influence of arterial structure and endothelial function on this relationship. Cross-sectional population-based study. One thousand and fifteen subjects randomly selected from the polling lists, were recruited by the Toulouse MONICA centre between 1995 and 1997. Carotid-femoral pulse wave velocity (PWV) and blood pressure (BP) were measured in the supine position. Common carotid intima-media thickness (IMT) and the presence of plaques were assessed by ultrasonography. sCD14 was measured using an immunoenzymatic method. The results concern the 891 subjects with complete data for all the variables. In the bivariate analyses, PWV (P < 0.001), systolic BP (P < 0.05), pulse pressure (PP) (P < 0.01), IMT (P < 0.001), the number of plaques (P < 0.05) and von Willebrand factor activity (vWFa) (P < 0.001) were positively associated with sCD14, whereas no significant relationship was observed between sCD14 and diastolic BP. After adjustment for age and sex, no significant relationship remained between IMT, the number of plaques, SBP, PP and sCD14. A significant and positive relationship was observed between sCD14 and PWV (trend P < 0.05) after adjustment for numerous confounders. This population-based study yields first evidence that sCD14 is associated with aortic stiffness independently of age, BP and atherosclerosis in humans.