The capillary barrier serves to protect cells from noxious materials bound to intravascular proteins and to regulate pressures and volumes of interstitial fluid, while allowing passage of essential substrates from the blood and the removal of metabolites. The permeability of capillaries to a solute depends on the anatomy of the capillary wall and the nature of the solute. The walls consist of monolayers of endothelial cells with characteristics peculiar to the individual organ: Most capillaries have openings between endothelial cells and some have holes through them. Hydrophilic and polar solutes traverse these “pores”, whereas lipid-soluble solutes can permeate the lipid bilayer or the endothelial cell membranes. For some solutes, special solute-specific transporter proteins in the cell membrane facilitate transfer across the membrane. For estimating permeability coefficients and determining the mechanism of permeation, tracer experiments done under varied circumstances are generally the most informative. Osmotic transient experiments, performed by changing osmolarity inside the capillary, require relatively complex analysis because there are simultaneous fluxes of both water and solutes.