Erythrocytes from 12 patients with homozygous sickle cell disease in the steady state were fractionated on a Percoll-Stractan density gradient. Erythrocyte deformability was measured by initial-flow-rate filtration through pores of 5 microns diameter and erythrocyte polymer content was calculated as a function of oxygen saturation. Density fractionated sub-populations of sickle cells showed distinct rheological characteristics, the filterability of dense cells being impaired by minimal oxygen desaturation with the apparent formation of little or no intracellular polymer. Lighter cell fractions required a greater degree of deoxygenation and polymer formation to impair deformability, although this occurred prior to morphological sickling. Dense cells therefore exert a disproportionate effect on blood rheology in sickle cell disease and are likely to have an adverse rheological effect in vivo at arterial oxygen tension.