We describe the importance of the low-density lipoproteins (LDL) used in preparing radioimmunoassay standard curves and the clinical application of monoclonal antibodies to LDL. LDL isolated from five normal men produced five parallel displacement curves with conventional mouse antiserum but there was a significant difference of immunoreactivity among the LDL. None of our four monoclonal antibodies could eliminate the heterogeneous immunoreactivity of different LDL. Thus, the determination of plasma apolipoprotein (apo) B will vary depending on the selection of LDL standards, and the comparison of absolute apo B values between laboratories will be of questionable value unless they use the same LDL standard. Nonetheless, in a radioimmunoassay our monoclonal antibody, LP-22, detected a more significant (p less than 0.0001) increase of plasma apo B in patients with angiographically documented coronary artery disease than did conventional antiserum (p less than 0.001). In addition, the overlap of apo B concentrations for patients with and without disease was less when monoclonal antibody LP-22 was used. We conclude that patients with coronary artery disease have a significant increase in the form of plasma apo B that is specifically recognized by LP-22 monoclonal antibody. Perhaps monoclonal antibodies will be able to sort out the various components of apo B, delineate their possible atherogenic roles, and offer us a predictive value for diagnosing such patients.