Cyclic oligomers of glucose, termed cyclodextrins (CDs), can contain 6 (alpha-CD), 7 (beta-CD) or 8 (gamma-CD) glucose units and are able to remove cholesterol from platelet membranes and decrease platelet aggregation. The present study was designed to examine the effects of these CDs on RBC aggregation and blood viscosity. Blood from normal adult volunteers was incubated at 37 degrees C with 3.0 x 10(-4) to 1.5 mM levels of the CDs, then processed to obtain platelet-rich plasma, platelet poor plasma and 40% hematocrit blood; measurements included collagen-induced platelet aggregation, RBC aggregation (Myrenne Aggregometer) and blood viscosity at 1-1000 sec(-1)(Rheolog). Our results indicate the expected dose-dependent inhibition of platelet aggregation by beta-CD, with no significant effects of alpha-CD or gamma-CD. RBC aggregation studies showed no effect of alpha-CD but highly significant (p<0.01) decreases by both beta-CD and gamma-CD; at the concentrations studied (1.5 x 10(-3) to 1.5 mM), beta-CD had somewhat greater effects. Blood viscosity was not affected by alpha-CD, but was significantly decreased in a dose-dependent manner by beta-CD and, at the highest concentration (1.5 mM), by gamma-CD. Interestingly, the effects of beta-CD and gamma-CD were independent of shear, with these effects not explained by the usual mechanisms. These results suggest the potential hemorheological value of CDs, yet also indicate the need for additional studies.