Here, we test the role of two other possible factors: 1) a reduced peripheral vasoconstriction (which may contribute because PD includes a generalized sympathetic denervation); and 2) an inadequate plasma volume (which may explain why plasma volume expansion can manage orthostatic hypotension in PD). We included 11 PD patients with orthostatic hypotension (PD ϩ OH), 14 PD patients without orthostatic hypotension (PD Ϫ OH), and 15 agematched healthy controls. Leg blood flow was examined using duplex ultrasound during 60°head-up tilt. Leg vascular resistance was calculated as the arterial-venous pressure gradient divided by blood flow. In a subset of 9 PD ϩ OH, 9 PD Ϫ OH, and 8 controls, plasma volume was determined by indicator dilution method with radiolabeled albumin ( 125 I-HSA). The basal leg vascular resistance was significantly lower in PD ϩ OH (0.7 Ϯ 0.3 mmHg·ml Ϫ1 ·min) compared with PD Ϫ OH (1.3 Ϯ 0.6 mmHg·ml Ϫ1 ·min, P Ͻ 0.01) and controls (1.3 Ϯ 0.5 mmHg·ml Ϫ1 ·min, P Ͻ 0.01). Leg vascular resistance increased significantly during 60°head-up tilt with no significant difference between the groups. Plasma volume was significantly larger in PD ϩ OH (3,869 Ϯ 265 ml) compared with PD Ϫ OH (3,123 Ϯ 377 ml, P Ͻ 0.01) and controls (3,204 Ϯ 537 ml, P Ͻ 0.01). These results indicate that PD ϩ OH have a lower basal leg vascular resistance in combination with a larger plasma volume compared with PD Ϫ OH and controls. Despite the increase in leg vascular resistance during 60°h ead-up tilt, PD ϩ OH are unable to maintain their blood pressure.Parkinson's disease; orthostatic hypotension; leg vascular resistance; plasma volume; head-up tilt SYMPTOMATIC AND ASYMPTOMATIC orthostatic hypotension (OH) is present in 30 -60% of patients with Parkinson's disease (PD) (15) and negatively correlated with quality of life (32). In elderly, OH is associated with cardiovascular morbidity and mortality (31, 33). The pathophysiology of OH in PD remains incompletely understood. Until now, the focus has been primarily on impairment of central mediated vasoconstrictor mechanisms. PD patients have a reduced baroreflex cardiovagal function, denervation of the heart, low norepinephrine levels, and no increment in norepinephrine levels during orthostatic challenges (14, 39). However, baroreflex failure and cardiac sympathetic denervation contribute to but cannot fully explain OH in PD (14, 16). During orthostatic challenges peripheral vasoconstriction contributes to maintain blood pressure via a central mediated vasoconstrictor mechanism, i.e., baroreflex, and local vasoconstrictor mechanisms, such as the venoarteriolar axon reflex (21) and the myogenic response (11). Since in PD a generalized rather than a central sympathetic denervation is present (40), central and local mediated peripheral vasoconstriction might be affected and, thereby, might play an important role in the pathophysiology of OH in PD.Furthermore, a lower plasma volume may be another contributing factor to OH in PD. This assumption is based on the important role of the s...