The objectives of the proposed research are to use biochemical and population genetic principles in order to: 1) define the genetic heterogeneity of human lysosomal acid lipase (LAL), and 2) determine whether genetic variation of this enzyme alters ones risk of developing atherosclerosis. Wolman's disease (WD) and cholesteryl ester storage disease (CESD) appear to represent a clinical spectrum due to mutation of LAL; both appear to have associated premature atherosclerosis. Using cell lines derived from a WD patient, her parents and a CESD patient, the investigators have developed a fluorometric assay for LAL and a fluorogenic method for the identification of LAL isozymes after electrophoresis. These methods have been adapted to peripheral lymphocytes which contain LAL; the lymphocytes of WD patients are deficient of LAL. A population survey with appropriate family studies will be conducted and the amount of quantitative or qualitative genetic variation determined. Correlation with risk of developing premature atherosclerosis will be determined in this group and a group of patients with premature atherosclerosis with positive family histories will be similarly studied.