There is a significant correlation between plasma levels of Lp(a) lipoprotein, coronary artery disease and the severity of atherosclerosis. The overall objective of this proposal is to develop a diagnostic test for Lp(a) by developing immunoassays specific for the Lp(a) antigen, apo(a) This remarkable overall sequence similarity between the Lp(a) antigen, apo(a), and the plasma protease plasminogen results in extensive immunological cross-reactivity. Currently available immunoassays are not specific for apo(a) for example, 24). Therefore, their suitability in assessing individual risk factors by quantitation of plasma Lp(a) levels appears questionable. The sequence similarity of apo(a) and plasminogen presents major problems for monospecific antibody production. Our strategy involves the use of synthetic peptides corresponding to unique regions of apo(a) which do not occur in plasminogen. Antibodies raised against these peptides will be used to develop a sensitive and specific assay for Lp (a) levels and the apo(a) isoforms. These assays will be utilized commercially as part of a panel of tests for the evaluation of relative risk for atherosclerosis. In addition, the synthetic peptides will be evaluated as chemically defined standards for these assays. The antibodies, specific for defined regions of apo(a), should also be useful for structural, biological and pathological studies of the Lp(a) antigen.