The pooling of blood in the limbs is the beginning of a chain of events which brings about the reflex syncope. Observations have confirmed that the reduction of plasma volume is also a factor pathogenetically determinant in the provocation of a faint. During orthostatic stress, plasma volume shifts towards the interstitial spaces of the infra-diaphragmatic vascular network, thus, contributing greatly to the reduction in the circulating volume. The aim of the present study was to calculate whether during orthostasis there was indeed a reduction in plasma volume and to what extent in a population at high risk for fainting. A comparative study of 50 recurrent fainters and 37 controls was performed. Each group was studied both in a supine (before) and orthostatic (after) position. Blood samples were taken to determine the hematocrit and hemoglobin values. The percentage variation of these values was calculated in order to obtain the reduction in plasma volume, i. e., the expression of the amount of plasma accumulated in the interstitial spaces. A significant difference in hematocrit and hemoglobin variation (before vs. after) was found between patients and controls. Plasma volume variation before vs. after (17.1 % in patients vs. 8.6 % in controls) was then calculated using these measurements. The difference in plasma volume variation between patients and controls can be interpreted as a co-factor together with the pooling of plasma in the pathogenesis of reflex fainting. This study illustrates an easy way to evaluate the role of plasma volume reduction in the pathogenesis of vasovagal syncope.