We hypothesized that during severe hemodilution (SH), i.e., hemodilution beyond 50%, the reduced conditions of shear stress result in endothelium dysfunction and subsequent vasoconstriction. To evaluate the endothelial responses associated with the reduction of hematocrit we tested the responsiveness of arterioles to acetylcholine. Infusion with high-molecular-weight dextran 500,000 following SH was characterized by laser Doppler flowmetry (LDF), total perfused capillary length (TPCL), vessel diameter, and red blood cell (RBC) velocity as visualized by fluorescence microscopy in the hamster cheek pouch. Hemodilution was performed by blood removal and simultaneous infusion of 6% dextran 70. LDF increased significantly during hemodilution in arterioles and in venules (100 +/- 20 vs 37 +/- 11 and 34.2 +/- 3.5 vs 28.6 +/- 4.0 perfusion units, PU, respectively). During the final step of hemodilution LDF decreased significantly to 12 +/- 4.5 PU in arterioles and 6.2 +/- 1.5 PU in venules, which correlated with the decrease of arteriolar RBC velocity. Arterioles constricted and TPCL decreased significantly (-35 +/- 5.3%). Hyperviscosity infusion significantly raised arteriolar and venular LDF to 184 +/- 15 and 40.2 +/- 3.5 PU, arterioles dilated, RBC velocity, TPCL, and mean blood pressure. There was an impairment of endothelial-dependent dilation that was not present in the group with dextran 500, which suggests that viscosity was involved in the development of vasoconstriction during SH. In conclusion, an increase in plasma viscosity has beneficial effects on the microcirculation during SH that might preserve arteriolar endothelium and capillary perfusion.