Introduction: The correction of hypovolemia with acellular fluids results in acute normovolemic anemia. Whether the choice of the infusion fluid has an impact on the maintenance of oxygen (O-2) supply during acute normovolemic anemia has not been investigated so far. Methods: Thirty-six anesthetized and mechanically ventilated pigs were hemodiluted to their physiological limit of anemia tolerance, reflected by the individual critical hemoglobin concentration (Hb(crit)). Hb(crit) was defined as the Hb-concentration corresponding with the onset of supply-dependency of total body O-2-consumption (VO2). The hemodilution protocol was randomly performed with either tetrastarch (6% HES 130/0.4, TS-group, n = 9), gelatin (3.5% urea-crosslinked polygeline, GEL-group, n = 9), hetastarch (6% HES 450/0.7, HS-group, n = 9) or Ringer's solution (RS-group, n = 9). The primary endpoint was the dimension of Hb(crit), secondary endpoints were parameters of central hemodynamics, O-2 transport and tissue oxygenation. Results: In each animal, normovolemia was maintained throughout the protocol. Hb(crit) was met at 3.7 +/- 0.6 g/dl (RS), 3.0 +/- 0.6 g/dl (HS P < 0.05 vs. RS), 2.7 +/- 0.6 g/dl (GEL, P < 0.05 vs. RS) and 2.1 +/- 0.4 g/dl (TS, P < 0.05 vs. GEL, HS and RS). Hemodilution with RS resulted in a significant increase of extravascular lung water index (EVLWI) and a decrease of arterial oxygen partial pressure (paO(2)), and O-2 extraction ratio was increased, when animals of the TS-, GEL-and HS-groups met their individual Hb(crit). Conclusions: The choice of the intravenous fluid has an impact on the tolerance of acute normovolemic anemia induced by acellular volume replacement. Third-generation tetrastarch preparations (e. g., HES 130/0.4) appear most advantageous regarding maintenance of tissue oxygenation during progressive anemia. The underlying mechanism includes a lower degree of extravasation and favourable effects on microcirculatory function.