The major apolipoprotein (apo) A-I containing lipoprotein, high- density lipoprotein, is a negative risk factor for cardiovascular disease. An atomic resolution molecular model for lipid-associated apo A-I was recently proposed in which two apo A-I molecules are wrapped beltwise around a small discoidal patch of phospholipid bilayer. Because of its detailed predictions of lipid-associated apo A-I structure, this molecular belt model, if confirmed, provides a blueprint for understanding the molecular mechanisms of reverse cholesterol transport, and thus for the rational design of new classes of drugs for reversal of atherosclerosis and cardiovascular disease. The details and implications of the model are currently being explored by site-directed mutagenesis. Copyright © 2000 Elsevier Science Inc.