In a cross-sectional study of 8695 men and women free of clinical CVD, aged 45-64 years at the 1987-1989 baseline Atherosclerosis Risk in Communities (ARIC) study exam, we examined the relationship between carotid artery lesions (CALs), with and without acoustic shadowing (AS) as an index of plaque mineralization, to systemic markers of inflammation and markers of endothelial function, including endothelial adhesion molecules. A three-level variable, based on the presence of extracranial CALs and AS, identified by B-mode ultrasound of six 1 cm arterial segments, defined the outcome. Among subjects without evidence of AS, after controlling for age, gender, ethnicity, study site, body mass index, hypertension, diabetes, and smoking status, CALs were associated with systemic markers of inflammation, including higher levels of fibrinogen [OR=1.24 (95% CI: 1.09, 1.40)] and white blood cell count [OR=1.37 (95% CI: 1.21, 1.56)]. Among subjects with a CAL, after controlling for the above risk factors as well as mean far wall intima-media thickness, AS was associated with higher levels of von Willebrand factor [OR=1.38 (95% CI: 1.10, 1.74)], a marker of endothelial activation. Associations with endothelial adhesion molecules were inconsistent. Further studies aimed at elucidating the mechanisms of arterial mineralization are warranted.