Hemodynamic responses to upright tilt were studied in eight young men at sea level (SL); after 1 h at 4,300 m simulated altitude (SA); and at 18 h, 66 h and 114 h during residence at 4,300 m (HA). Heart rate (HR), stroke volume (SV), cardiac output (CO), calf blood flow (CBF), blood pressure (BP) and total peripheral resistance (TPR) were obtained during supine rest and after 13 min of 60 degrees head-up tilt using an impedance monitor and electrosphygmomanometer. SL to HA changes in blood volume (BV) were calculated from hematocrit and hemoglobin values. Plasma norepinephrine (Nor) was measured at SL and after 18 h and 66 h of HA. Supine HR, TPR and BP were increased while SV, CO and CBF were reduced SL to HA (p less than 0.05). HR and BP in the upright position were increased SL to HA (p less than 0.05). The responses to tilt (delta supine to upright) were unaltered SL vs SA. With prolonged exposure, SV, CO, TPR and CBF responses to tilt were reduced (p less than 0.05). The reduced responses to tilt at HA were associated with a 10% decline in BV (p less than 0.01) and a 40% increase in Nor (p less than 0.05). It was concluded that the reduction in SV during tilt at SL and SA was compensated for by increases in HR and TPR in order to maintain BP. After 18 h HA, BP in the upright position was maintained only by an increase in HR.