The blood-brain barrier (BBB) serves to regulate passage of solutes and water between circulating blood and brain extracellular fluid (1 ,2 ). It is composed of endothelial cells that line brain capillaries and exhibit selective transport properties. Cerebral endothelial cells are unusual in that they possess true tight junctions (zonula occludens ), which provide a relatively high electrical resistance, and impart polarity to the plasma membrane (3 ,4 ). The presence of tight junctions limits the movement of solutes through the intercellular space, and separates the plasmalemma into luminal (blood-facing) and abluminal (brain-facing) plasma membrane domains. Thus, penetration of the BBB is for the most part transcellular, and requires transport across the respective plasma membrane domains (5 ,6 ).