Exposure to microgravity in humans causes cardiovascular deconditioning affecting blood pressure, heart rate and vascular responsiveness. This study investigated cardiac output, arterial blood pressure and regional blood flows [radioactive microspheres: 57Co, 15.5 (SEM 0.1) microm in diameter] in conscious and freely moving rats subjected to 14 days of simulated microgravity (head-down suspension, HDS) in male Wistar rats: control (horizontally attached, n = 7), suspended for 14 days (n = 8) and suspended/allowed to recover for 10 min (R10min, n = 5) or 24 h (n = 9). Compared to the control group, 14 days of HDS resulted in reduced total peripheral resistance (37%); an increased cardiac index (65%) was associated with no significant change in the mean arterial pressure BPa. There were elevated brain (63%), visceral (> 20%), hindlimb (> 80%) and forelimb (> 215%) muscle blood flows. In the R10min group, the BPa decreased (18%) and the regional blood flows returned to control values. Within 24 h the BPa as well as cardiac index and total peripheral resistance were restored. In conclusion, 14 days of HDS engendered local circulatory changes resulting in transient blood pressure instability during recovery.