We present theoretical and experimental arguments supporting the hypothesis that the cell surface glycocalyx may negatively regulate adhesive phenomena. First, it is recalled that a repulsive interaction of several thousands of piconewtons may be generated on a contact area of about 1/100 gm 2 by a combination of electrostatic and entropic forces (steric stabilization). Second, electron microscopical data are reported to provide an estimate of the thickness of the cell coats of murine macrophages and sheep erythrocytes made phagocytable by exposure to glutaraldehyde or specific antibodies. Using conventional carbohydrate staining procedures, it is shown that the total thickness of the electron-dark regions in areas of intercellular contact is lower than the sum of the thicknesses of electron-dark regions on free cell areas. Further, removing negative charges with neuraminidase or neutralizing these charges with polylysine may reduce intermembrane distance in contact areas. Third, it is shown that a decrease of erythrocyte surface charges with neuraminidase increases their adhesion to murine phagocytes under dynamic, not static conditions. It is concluded that a major determinant of steric stabilization is the relative length of adhesion molecules and surface repeller elements, and that repulsion is particularly important under dynamic conditions. Thus, dynamic effects must be included in models of steric stabilization.