The prevalence of the metabolic syndrome (MS) is rapidly growing, especially in women. This analysis was designed to evaluate whether preclinical vascular changes are detectable in middle-aged women with the MS. Five thousand sixty-two women participated in a prospective study of the causes of cardiovascular disease in women (the "Progetto Atena" study). Three hundred ten women underwent high-resolution B-mode ultrasound examinations. Common carotid intima-media thickness (IMT) and internal and external diameters were measured using a computerized system. The National Cholesterol Education Program Adult Treatment Panel III criteria were used to classify participants as having the MS. Seventy-three subjects fulfilled the criteria for the MS. Women with the MS were slightly older and had greater serum total cholesterol and higher levels of serum insulin and lipid peroxidation compared with women without the MS. The group with the MS had a greater mean IMT (1.24 +/- 0.27 vs 1.10 +/- 0.20 mm, p <0.0001) and larger mean values for diameters (7.9 +/- 1.0 vs 7.4 +/- 0.7 mm, p <0.0001 for external diameter; 6.1 +/- 0.8 vs 5.8 +/- 0.6 mm, p <0.005 for internal diameter). The average increase in wall thickness was greater than in vessel diameter, as evidenced by the greater relative wall thickness in women with the MS (0.41 +/- 0.09 vs 0.38 +/- 0.07, p <0.005). In conclusion, carotid structural changes are noninvasively detectable in asymptomatic middle-aged women with the MS. These modifications indicate a dynamic process of arterial remodeling by which the vascular system responds to atherosclerotic stimuli.