Beginning in 1987 and using blood samples and data from the RFHS, variation at the DNA level was determined using restriction fragment length polymorphisms and at the protein level by isoelectric focusing. The relationships were defined in the population among the apolipoproteins, cholesterol, triglycerides, high density lipoprotein cholesterol phenotypes and estimates were done on the effects of age, sex, smoking, drug use, and obesity on these relationships. Estimates were determined for the fraction of interindividual variation in the apos attributable to gene loci coding for these molecules. Estimates were also determined for the fraction of interindividual variation in cholesterol, triglycerides, and high density lipoprotein cholesterol attributable to gene loci coding for the apos and the LDL receptor. A determination was also made as to whether genotypic variation for the gene loci coding for the apo and LDL-receptor contributed to the prediction of coronary heart disease beyond that provided by the effects of these gene loci on the interindividual variation in the apos, cholesterol, triglycerides, and high density lipoprotein cholesterol. Radioimmunoassay and medical information collection took place at the Mayo Clinic. DNA probes, DNA studies of special families, and definition of new restriction fragment length polymorphism took place at Charing Cross Hospital in London, England. RFLP typing of genes coding for the apolipoproteins and the LDL receptor and electrophoretic typing of the known apo E and AIV protein polymorphisms took place at the University of Pittsburgh. The genetic architecture responsible for phenotypic variability in the population at large was defined at the University of Michigan and Washington University, St. Louis.