To determine whether selectin-mediated leukocyte-rolling velocity in inflamed venules in vivo is determined by wall shear rate (WSR) or by wall shear stress (WSS). WSS was manipulated independently of WSR by altering the viscosity of blood plasma in mice with an isovolemic exchange of blood for low- or high-viscosity dextran solutions. Rolling of neutrophils or beads coated with P-selectin glycoprotein ligand-1 (PSGL-1) was reconstituted on P-selectin immobilized on the wall of a parallel plate flow chamber at two different viscosities of the perfusion medium. Leukocytes in vivo showed no increase in rolling velocity when shear stress was doubled by doubling viscosity. Neutrophils in the parallel-plate flow chamber in vitro showed the same dependence on WSR as leukocytes in vivo, but bead-rolling velocities correlated best with WSS. Rolling leukocytes, but not beads, deformed significantly in shear flow, and deformation correlated better with WSS. These data suggest leukocyte deformation during rolling offsets increased bond breakage at higher shear stress. The stable rolling velocity allows sufficient surveillance of the endothelial surface, even in venules with high WSS. doi:10.1038/sj.mm.7800165