The electrophoretic mobility of human red blood cells treated with protease enzymes (papain, bromelin and ficin) was measured as a function of enzyme concentration and electrolyte concentration of the medium. The results are analyzed via an electrophoretic mobility formula for “soft particles” (i.e. particles covered with a surface layer of polyelectrolytes). This mobility formula involves two parameters, the fixed charge density (N) and a parameter 1/λ characterizing “softness” of the cell surface layer. It is found that both parameters, plotted as a function of protease concentration, exhibit a steep change around the critical protease concentration at which the cell mobility decreases abruptly and the cells become agglutinable (N decreases and 1/λ increases). The decrease in N accounts for the observed decrease in cell mobility. The increase in 1/λ suggests that the protease treatment leads to removal of glycoproteins from the surface layer, including not only their charged portions (sialic acid) but also their uncharged portions, making void spaces in the cell surface region.