Due to their special position at the tissue-blood interface, the endothelial cells are endowed with two mechanisms for handling plasma molecules: one, receptor-mediated endocytosis, which supplies nutrients for the cell's own metabolic needs; the other, direct transendothelial transport of material from plasma to the intima of arteries. Under normal physiological conditions, the latter transendothelial pathway is far more important than the endocytic one. Routes for exchange of both small and large plasma molecules include the clefts between adjacent endothelial cells (paracellular) and plasmalemmal vesicles. Paracellular transport is restricted to molecules smaller than 4 nm in diameter, and is the pathway for water filtration. Larger molecules, as large as 30 nm in diameter, are transported through plasmalemmal vesicles. Changes in endothelial permeability occur during inflammation, hypertension or diabetes.