Plasma volume (PV) decreases at high altitude, but is rapidly restored upon return to sea-level (RSL). The aim of this study was (1) to describe PV recovery upon RSL with concomitant changes in major fluid regulating hormones, and (2) to test the hypothesis that PV recovery is promoted by the administration of a plasma expander. Ten male subjects were evaluated at rest and during submaximal exercise at sea-level (SL), after 7 days at 4,350 m (H7), and on RSL, on day 1 (RSL1, rest only) and day 2 (RSL2). PV (measured by carbon monoxide rebreathing), plasma renin (Ren), aldosterone (Aldo), atrial natriuretic factor (ANF) and arginine vasopressin (AVP) were measured at rest and during exercise. The subjects were divided into two groups 1 h before RSL, one group receiving PV expansion (475+/-219 ml) to ensure normovolemia (PVX, n=6), the others serving as controls (Control, n=4). PV decreased by 13.6% in H7 ( n=10), but was restored in RSL2, regardless of PVX. Ren, Aldo and AVP, which were similar in both groups, were reduced in H7, but were higher in RSL2 (rest or exercise). ANF was modified neither by hypoxia nor by PVX. Total water intake was reduced in H7, but remained normal in RSL in both groups, whereas water output dropped in RSL. PVX increased urine flow rate in RSL1 compared with subjects not given PVX. The present results suggest that PV recovery during early RSL is mainly due to a decreased diuresis, promoted at least in part by changes in fluid regulating hormones. However, neither PV recovery, nor hormonal responses were altered with PVX-induced normovolemia upon RSL.