We evaluated the usefulness of measurements of the inferior vena cava (IVC) diameters on abdominal echograms as an indicator of changes of venous return in subjects with orthostatic intolerance (OI) induced by simulated microgravity. We performed a standing test and recorded the IVC diameters on abdominal echograms in 12 subjects placed on a 20-day 6 degree head-down tilting bed rest experiment. We found that different patterns of changes in IVC diameter occurred in the standing test on Day 10 of the experiment; in five subjects with a marginal decrease in pulse pressure, IVC diameters in the upright position were markedly decreased compared with those in the supine position. In five subjects with feelings of discomfort, the IVC diameters in the upright position distended or did not decrease from those in the supine position. These results suggested that the changes in IVC diameter on the standing test indicated the presence of various types of hemodynamic responses of OI caused by simulated microgravity. In this study we also evaluated changes in body-water compartments by conducting multi-frequency bioelectrical impedance analysis. Longitudinal data analysis showed that the total body water/fat-free mass and extracellular fluid/fat-free mass decreased during the experiment period and recovered thereafter, and that the intracellular fluid/fat-free mass decreased during the experiment. No significant difference in changes in body-water compartments was seen among subjects with different patterns of changes in IVC diameters. Measurement of IVC diameter was useful to estimate hemodynamic changes in subjects with OI.