Human plasma low density lipoproteins (LDL) represent the major carrier of cholesterol in the circulation. LDL consist of approximately 75% lipid and 25% protein. The major lipids are cholesteryl esters, unesterified cholesterol and phospholipid; phosphatidylcholine acounts for 75% of the total phospholipid, with sphingomyelin accounting for the remainder. The major protein constitutent of human plasma LDL is apolipoprotein B (apoB). In addition to binding and transporting lipids, apoB plays an important role in lipoprotein metabolism by its interaction with specific cell surface receptors. The long-range objectives of this research are to define the structural domains of apoB and, in particular, the amino acid sequence domains of apoB which interact with cell surface receptors on fibroblast and T-lymphocytes, and with heparin. The methods include techniques of protein chemistry, amino acid sequencing, physical chemistry, cell biology and immunochemistry. In addition, the relationship of these domains to LDL structure and metabolism will be assessed. It is anticipated that detailed knowledge of the structure of apoB and the relationship of structure to function will contribute to our overall understanding of the factors which regulate the metabolism of human plasma LDL. Since LDL lipids are the major contributor to aterosclerotic lesion, it will then be possible to understand the basic processes of atherosclerosis.