Use of bed rest to simulate microgravity exposure is not well validated. We compared heart rate (HR) and blood pressure (BP) responses to standing in bed-rest (BR) subjects (n=11) to those of two astronaut groups. One astronaut group (n=28) fluid loaded (FL) before landing by consuming a water and salt tablet mixture, the second astronaut group (n=8) did not (NL). Bed-rest or microgravity exposure lasted approximately 7.0 days. Preexposure, the responses to standing did not differ between groups. Postexposure, all groups demonstrated an increased HR response (p<0.01), a decreased SBP response (p<0.05), no change in DBP response, and a reduced PP response (p<0.05) compared to preexposure. Change in HR response was lowest for the FL group, presumably due to increased plasma volume induced by fluid consumption. These findings generally support bed rest as a valid simulator of microgravity.