A complete description of the pathophysiology of sickle cell disease requires a physiologically meaningful measurement of red cell deformability. We have designed and built a system which allows one to determine filtration characteristics of erythrocytes. A dilute red cell suspension is forced through a 3.0-micron polycarbonate Nuclepore membrane with a constant positive pressure of 20 mm Hg. Under these conditions blockage of the pores in the polycarbonate membrane is insignificant and flow is linear. We use the relative number of cells filtered through the membrane as a means of approximating the means deformability of cells in the suspension. Using this system we have compared erythrocytes from various mammals and shown that our technique is sensitive in detecting not only differences in cell deformabilities between mammalian species but also changes in cell deformability of human red cells due to exchange transfusion and application of drugs. There was a positive correlation between cell filtrability and percentage cell recovery (coefficient of correlation, 0.65) and a negative correlation between cell size and filtrability (coefficient of correlation, -0.61). The filtrabilities of normal volunteers and sickle cell disease patients were found to be 71.8 +/- 6.6 and 53.6 +/- 5.0%, respectively. This system is sensitive and reliable, and should be useful in evaluating both the contribution of filtrability to the viability of red cells in vivo and potential therapeutic agents for sickle cell disease.