Viscosity (eta) in a blood suspension is affected by the total hematocrit (HT) as well as by the deformability of the cells. The impact of these combined factors on the rheologic behavior of sickle cell suspensions and on guidelines for transfusion has not been explored fully. Therefore, the eta of mixtures of washed normal (AA) and sickle (SS) red cells was determined in a rotational viscosimeter as a function of the hematocrit level of SS cells (HS), HT, oxygen tension (PO2), and shear rate. The ratio HT:eta can be taken as an index of potential oxygen delivery. The optimal HT (for maximum HT:eta) became progressively higher as the HS or the HS:HT ratio was lowered: at a given HT, HT:eta rose with a decrease in HS, especially at low HS values. These data support the concept that simple transfusion alone is not as beneficial to the patient as exchange transfusion and that substantial benefit can be obtained by bringing the patient to very low HS levels. The finding that eta rose with HT more steeply when the HS:HT ratio rather than HS was held constant suggested that the absolute level of HS may be more useful than the HS:HT ratio as a guide for a transfusion regimen.