Extreme hemodilution was performed in the hamster chamber window model using 6% dextran 70 kDa lowering systemic hematocrit by 60%. Animals were subsequently divided into 3 groups and hemodiluted to a hematocrit of 11% using: 6% dextran 70 kDa, 6% dextran 500 kDa, and a 4% dextran 70 kDa + 0.7% alginate solution (n = 6 each group). Final plasma viscosities were 1.4 ± 0.2 cp, 2.2 ± 0.1 cp and 2.7 ± 0.2 cp, respectively, (P< 0.05, high viscosity vs. low viscosity). Blood viscosities were 2.1 ± 0.2 cp, 2.9 ± 0.4 cp and 3.9 ± 0.3 cp, respectively. The lowest blood and plasma viscosity group had a significantly lower functional capillary density, 37 ± 16%, while the two high viscosity solutions were 71 ± 15% and 76 ± 12% (P < 0.05, high viscosity vs. low viscosity), respectively. Arteriolar and venular flow in the dextran 500 kDa and alginate groups were higher than baseline (i.e., normal non-treated animals) while the low viscosity group showed a reduction in flow. These microvascular changes were paralleled by changes in base excess which was negative for the dextran 70 group, and positive for the other groups. However, tissue pO₂ was uniformly low for all groups (average of 1.4 mmHg). Calculation of tissue oxygen consumption in the window chamber based on the microvascular data, flow and intravascular pO₂, showed that only the alginate + dextran 70 kDa exchanged animals returned to baseline oxygen consumption, while the other groups were lower than baseline (P < 0.05). These results show that hemodilution performed with high viscosity plasma expanders yields systemic arterial pressures and functional capillary densities that are significantly higher (P < 0.05) than those obtained with 6% dextran 70 kDa, a fluid whose viscosity is similar to that of plasma. A condition for obtaining these results is that oncotic pressure of the plasma expander be titrated to near normal, so that autotransfusion of fluid from the tissue into the vascular compartment does not reduce the effects of increasing plasma viscosity and increased shear stress on the microvascular wall.