Hyperhomocysteinemia has been reported to be associated with both vascular structure alteration and increased cardiovascular risk. This study examined whether hyperhomocysteinemia causes increased systemic arterial stiffness, thereby enhancing blood pressure response to stress in hypertensive patients. In 50 treated hypertensive patients, we studied brachial-ankle pulse wave velocity (PWV), a new measure for arterial stiffness, blood pressure response to stress, and blood pressure recovery after stress. Autonomic nervous activities were examined by spectral analysis of blood pressure and RR interval variabilities. Total plasma homocysteine and neurohumoral parameters were determined from fasting blood. Brachial-ankle PWV correlated with age (r=0.64, p<0.001), plasma homocysteine concentration (r=0.35, p<0.05), and systolic blood pressure (SBP) (r=0.62, p<0.001). Higher plasma homocysteine concentration was independently associated with greater brachial-ankle PWV (beta=0.388, p=0.01). We classified the subjects into high homocysteine (7.3 nmol/ml or over) and low homocysteine (7.2 nmol/ml or below) groups. Baseline SBP, plasma renin activity, aldosterone, and norepinephrine concentrations were similar between the two groups. However, the SBP values during stress and the recovery periods were higher in the high homocysteine group than the low homocysteine group even after adjusting for sex and age. The behavior of sympathetic vasomotor activity did not differ between the two groups. These data suggest that higher plasma homocysteine concentration is associated with increased systemic arterial stiffness, which may enhance blood pressure reactivity to stress in hypertensive patients.