Receptor-mediated cell adhesion to surfaces depends on the motion of the cell prior to adhesion. We studied the hydrodynamic behavior of cells near a wall in simple shear flow using a model leukocyte system that we have also used extensively in cell-substrate adhesion studies. Specifically, we measured the velocity of rat basophilic leukemia (RBL) cells near a surface in a parallel-plate flow chamber and compared it to the motion of polystyrene beads and glutaraldehyde-fixed RBL cells. We found that RBL cells (13 mu m diameter) travel 25 % faster than polystyrene beads of 14.5 mu m diameter for a wide range of shear rates (20-180 s(-1)); this suggests that RBL cells would travel 39 % faster than polystyrene beads of equivalent size. Glutaraldehyde-fixed RBL cells travel at a velocity between those of live cells and 14.5-mu m beads. These differences in velocities have been observed over both polyacrylamide gel and glass substrates. Application of a theory for hard sphere motion near a wall in simple shear flow at low. Reynolds number [Goldman, A. J.; Cox, R. G.; Brenner, H. Chem. Eng. Sci. 1967b, 22, 653-660] to our measured cell velocities suggests that cells are separated from the wall by greater than or equal to 550 nm. Such large separation distances have also been predicted by others who have used hard sphere theory to analyze the effect of shear flow on cell motion near walls. However, the extensive receptor-mediated cell adhesion seen in these systems is inconsistent with these separation distances, which are similar to 30 times greater than the distance required for receptor-ligand contact. Instead, we propose that, because of cell deformability and cell surface roughness, cells remain within a separation distance that allows for molecular contact while they travel faster than the hard sphere theory predicts. Therefore, the theory of Goldman and co-workers, while adequate for hard sphere motion, is likely not accurate for cellular motion.