Objective. To study the effects of hypovolemia on cardiovascular response to orthostatic stress, and to investigate the role of hypovolemia in the mechanism of cardiovascular deconditioning and orthostatic intolerance induced by space weightlessness. Method. The effects of loss of blood volume had been incorporated in the sub-model of blood redistribution in the model developed for simulating the cardiovascular response to lower body negative pressure (LBNP). With the help of the model, we simulated the changes of heart rate (HR) and blood pressure (BP) during LBNP after 0-25% loss of blood volume. Result. When the amount of decrease of blood volume was less than 5% of the total blood volume, HR and BP could be maintained in normal range during LBNP through baroreflex regulation. When the amount of the decrease of blood volume was more than 15% of the total blood volume, HR and BP could be kept in normal range when the subject was supine and at rest. But BP fell sharply and the cardiovascular system almost collapsed during orthostatic exposure. Conclusion. Decrease of blood volume causes significant degradations of cardiovascular response to orthostatic stress.