The rheological properties of erythrocytes of 14 patients with iron deficiency anemia were studied by filtration of cells through polycarbonate filters with a nominal pore diameter of 5 micron and by viscosity measurements of erythrocyte suspensions with a hematocrit of 80%. Erythrocytes of the patients passed through the filter pores more slowly than the cells from controls. The diminished deformability of the erythrocytes of the patients was solely due to an unfavorable ratio of cell surface area to microcytic cell volume. The viscosity of the ghost suspensions of the patients showed a normal flexibility. The hemoglobin content of the isolated ghosts was diminished, indicating an increased hemoglobin fluidity in the interior of the intact cells. The viscosity of erythrocytes of the patients was slightly increased at low shear rates but was normal at intermediate and high shear rates. We suggest that the decreased erythrocyte flexibility of microcytosis at low shear rates is no longer present at higher shear rates because of an increased fluidity of the intracellular hemoglobin. We discuss whether or not this mechanism also operates in vivo. The in vitro diminished deformability of erythrocytes explains the shortened survival of the patients' erythrocytes in vivo.