Using intravital microscopy of the rat cremaster muscle, we studied the effects of changing red blood cell (RBC) aggregation on RBC arteriolar velocity and perfused capillary density (PCD). To modify RBC aggregation, 2 and/or 10% dextran (molecular weights 40,000, 70,000 or 480,000) or fresh rat plasma was infused into adult male rats via a normovolemic hemodilution procedure. The high-molecular-weight dextrans (70,000 and 480,000) both induced RBC hyperaggregation associated with similar dose-dependent decreases in RBC arteriolar velocity (30 and 40% for dextran concentrations of 2 and 10%, respectively) and in PCD (35 and 37%, respectively, for the two concentrations). Conversely, with 40,000 molecular weight dextran or plasma, we observed a 30% increase in RBC arteriolar velocity, but no change in PCD or hyperaggregation. Intravenous injection of the antiaggregating drug troxerutin (10-3M), either before or after 2% dextran 70,000, significantly inhibited the effects of this dextran on RBC arteriolar velocity and on PCD. We conclude that RBC hyperaggregation can lead to changes in both arteriolar velocity and PCD and may, therefore, impair tissue oxygenation.