The metabolic syndrome (MetS) is associated with increased risk of type-2 diabetes and cardiovascular disease (CVD). We hypothesized that both small and large arteries may be impaired in subjects with the MetS, even in the absence of known CVD or diabetes. We compared both skin capillary density (CD) and pulse-wave velocity (PWV) in 36 cases with the MetS with those from 108 age- and gender-matched controls from the SU.VIM.AX-2 cohort. Compared with controls, MetS subjects demonstrated increased PWV (12.2+/-2.8 vs. 10.7+/-1.9 m s(-1), P=0.005) and lower functional CD (83.1+/-15.7 vs. 89.4+/-14.2 capillaries per mm(2), P=0.03). Functional CD was inversely related to fasting glucose, triglycerides (TGs) and HOMA-IR (all P<0.05). On the other hand, no association was found between CD and BP or with PWV. In multivariate models, the odds ratios (95% confidence interval) for one standard deviation change, for having an impaired PWV (>or=12 m s(-1), n=44), were: 1.65 (1.11-2.45) for systolic BP and 1.93 (1.25-2.99) for TG only. For impaired CD (<or=80 capillaries per mm(2)), the odds ratios (95% confidence interval) were 1.45 (1.00-2.08) for TG and 1.65 (1.13-2.43) for fasting glucose, only. In conclusion, MetS subjects exhibited evidence of macro- and microcirculatory dysfunction, even in the absence of diabetes and CVD. The common mechanism linking MetS components to CVD risk through small- and large-artery dysfunctions may be mediated through metabolic factors related to insulin resistance, not to increased BP.