This is a closely integrated program which intensively investigates lipoprotein interactions with one another and with various cells and tissues of the body, as well as how lipoproteins are produced and gain access to and accumulate in the artery wall, there to affect the cell metabolism. The individual Rhesus monkey is the focus of many of our studies. These central concerns will be approached at several levels--the structure and the interactions of individual lipoproteins and lipoprotein subclasses; the heterogeneity of their component apoproteins; the in vivo and in vitro formation and metabolism of apoproteins and lipoproteins by the liver, the intestine and within the plasma compartment; the controlling factors in the assembly and intracellular transport of nascent VLDL, the precursor of plasma LDL; the familial and nutritional determinants of lipoprotein profiles in vivo emphasizing the differential response of individual animals to high fat challenge with particular attention to the molecular basis of these; the specificity determinants of the interaction of lipoproteins and lipoprotein subclasses with cells of the artery wall and liver; the effects of lipoproteins and lipoprotein subclasses on the smooth muscle cells and macrophages in tissue culture; the effects of hemodynamic factors in modulating the influence of lipoproteins on the artery wall and on cells in culture; the determinants of lipoprotein size in normal and hyperlipidemic animals. Major emphasis is given to the heterogeneity within the major classes of lipoproteins and apoproteins, whether these are controlled by genetic, nutritional, and biosynthetic or other metabolic determinants.