The present study investigated the effects of the osmotic environment on the rheological properties of erythrocytes and their suspensions. In an iso-osmotic medium, erythrocytes forming a biconcave discocyte under resting conditions, exhibited high deformability. In a low-osmotic medium, the deformability of erythrocytes, which swelled and exhibited a spherical shape, significantly decreased at a high shear stress and the high-shear viscosity of the cell suspension was slightly higher than that of normal blood. Hyper-osmotic stress, however, which caused to form echinocytes, decreased cell deformability but exhibited smaller viscosity in low shear rates than iso-osmotic blood viscosity. These results showed a close relation with the aggregability measurements, in that hypertonic blood showed lower aggregability than the hypotonic and isotonic RBC suspensions. These findings indicate that the physicochemical environment has a strong influence on the rheological properties of the erythrocyte and its suspensions.