This study was carried out to determine the effect of -6˚ head-down bedrest on the cardiovascular and hormonal responses to orthostasis and to evaluate the mechanism of orthostatic intolerance. Ten healthy young men were changed the body position from -6˚ head-down or supine bedrest for 2 hr to 70˚ head-up tilt for 20 min. During the bedrest, there were no differences in hemodynamic and hormonal changes between the head-down and the supine positions. However, the tendency of decreased end-diastolic volume and increased cardiac contractility during the later period of 2 hr showed that the cardiovascular adaptation could be accelerated within a relatively short period in the head-down bedrest. During the head-up tilt, presyncopal signs were developed in five subjects of the supine bedrest, and one of the same subjects of the head-down bedrest. In the tolerant subjects, the increase in cardiac contractility and plasma epinephrine level during the bend-up tilt was greater following the head-down bedrest than that following the supine bedrest to compensate for reduced venous return. The intolerant subjects showed the greater decrease in end-diastolic and stroke volume, and the greater increase in heart rate during the head-up tilt than the tolerant subjects. Cardiac contractility and plasma epinephrine level were remarkably increased. However, arterial pressure was not maintained at the level for the appropriate compensation of the reduced venous return. It seems that the tolerance to orthostasis is more effective after the short-term head-down bedrest than after the supine bedrest, and the secretion of epinephrine induces the higher cardiac performance as a compensatory mechanism fur the reduced venous return during the orthostasis following the head-down bedrest than the supine bedrest.