The initial step of reverse cholesterol transport, the efflux of cell cholesterol into the extracellular fluid, has received much attention over the past year. Some studies have provided insights into the mechanism of cholesterol efflux and others have focused on the identity of the extracellular acceptors of cell cholesterol. Attention has also been directed towards the influence of HDL composition on the ability of these lipoproteins to accept cell cholesterol. There have been several studies addressing the importance of pre-[beta]-migrating HDL and of lipid-free apolipoproteins as acceptors of cell cholesterol. On the basis of these and earlier reports, a hypothetical cycle is proposed in which lipid-free apolipoprotein Al dissociates from plasma HDL and transfers into the interstitial space where it acquires phospholipids and cholesterol from cells and becomes a discoidal HDL. Discoidal HDL transfer via lymphatics to the plasma where they are converted into mature HDL, thus completing the cycle.