Upright posture and lower body negative pressure (LBNP) are used to produce orthostatic stress. However, regional circulatory responses to postural changes and LBNP may differ. Therefore we studied regional blood flow and blood volume changes in ten healthy subjects undergoing graded lower body negative pressure (-10 to -50 mm Hg) and eight subjects undergoing incremental head-up tilt (HUT), (20°, 40° and 70°) on separate days. We continuously measured BP, HR, and regional blood volumes and blood flows in the thoracic, splanchnic, pelvic and leg segments by impedance plethysmography (IPG) and calculated regional arterial resistances. Neither LBNP nor HUT altered systolic BP while pulse pressure decreased significantly. Blood flow decreased in all segments, while peripheral resistances uniformly and significantly increased with both HUT and LBNP. Thoracic volume decreased while pelvic and leg volumes increased with HUT and LBNP. However, splanchnic volume changes were directionally opposite with step-wise decreases in splanchnic volume with LBNP and step-wise increases in splanchnic volume during HUT. Splanchnic emptying in LBNP models regional vascular changes during hemorrhage but does not model orthostasis in which gravitationally driven splanchnic filling occurs. Splanchnic filling may limit the ability of the splanchnic bed to respond to thoracic hypovolemia during upright posture.