High density lipoproteins are a heterogeneous mixture of spherical macromolecules which differ in size (80-120 A), chemical composition (apolipoprotein A-I: 30-35%; apolipoprotein A-II: 10-15%; apolipoprotein C: 3-5%; phospholipids 25-30%; cholesterol/cholesterol esters: 15-20%; triglycerides: 3-5%) and physico-chemical properties. They can be isolated through selective precipitation of apolipoprotein B-containing lipoproteins (very low density lipoproteins, low density lipoproteins, lipoprotein (a)) and, under routine conditions, quantitation can be performed by the determination of their cholesterol or apolipoprotein content. A considerable portion of high density lipoproteins originates in plasma from discoidal phospholipid-apolipoprotein bilayers (thickness: 46 A; diameter: 190 A). These bilayers are in part synthesized by the liver and in part derived from the surface of chylomicrons during lipolysis. The role of discoidal precursors of high density lipoproteins in cholesterol-uptake from peripheral cells will be discussed.