Endothelial cells regulate vascular tone and mural remodelling in a shear-dependent manner that is commonly assumed to keep wall shear stress constant across arteries and species. Allometric arguments show that aortic flow velocity is constant across species, a deduction that is consistent with much experimental data, but the same arguments also show that the shear stress experienced by aortic endothelium will depend inversely on body mass to the 3/8th power, and hence will be 20-fold higher in mice than in men. This conclusion is robust and has important implications for the study of shear-dependent vascular biology and pathology.