Although vasovagal syncope (VVS) is a common clinical condition the underlying pathophysiology is not fully understood. A decrease in cardiac output has recently been suggested as a determinant factor for orthostatic VVS. The aim was to investigate compensatory mechanisms to maintain central blood volume and venous return during hypovolemic stress in women with VVS. 14 VVS women (25.7±5.0 years) and 15 matched controls (22.8±3.2 years) were investigated. Single step and graded lower body negative pressure (LBNP) to presyncope was used to create hypovolemic stress. Peripheral mobilization of venous blood from the arm (capacitance response and net capillary fluid absorption) and lower limb blood pooling (calf capacitance response) were evaluated with volumetric technique. Cardiovascular responses and plasma norepinephrine (P-NE) were measured. Resting P-NE was elevated in VVS (P<0.01). Despite similar hypovolemic stimulus, VVS displayed blunted increase in P-NE (P<0.01) and reduced maximal percentage increase in TPR (P<0.05) during graded LBNP. Arm capacitance response was slower (P<0.05) and reduced in VVS at higher levels of LBNP (P<0.05). Capillary fluid absorption from extra- to intravascular space was reduced by almost 40% in VVS (P<0.05). Accordingly, a more pronounced reduction in CO was found (P<0.05). In conclusion, women with VVS presented with decreased mobilization of peripheral venous blood and decreased net fluid absorption from tissue to blood during hypovolemic stress, partly explained by an attenuated vasoconstrictor response. This may seriously impede maintenance of cardiac output during hypovolemic stress and could contribute to the pathogenesis of VVS.