S era from patients with extrahepatic biliary obstruction were found to have an abnormal lipoprotein (obstructive lipoprotein) which failed to react with antibodies to normal lipoproteins of d < 1.063. Preparations of this abnormal lipoprotein made by a combination of immunoprecipitation and multiple polyanion precipitations revealed a high content of free cholesterol (26%) and phospholipids (61%) but only trace amounts of cholesterol esters and triglycerides. Protein content varied from 13% to a corrected low of 5% when ultracentrifugation was also performed. Amino acid analyses of the latter preparations resembled that of lipoproteins of d < 1.006.The reasons underlying the apparent unreactivity of the abnormal lipoprotein were explored. No evidence could be found for soluble antigen-antibody complexes of γ-globulin and the abnormal lipoprotein, nor for inhibition of antigen-antibody complex formation by serum factors. Purified preparations of obstructive lipoprotein did not react with antisera to high- or low-density lipoproteins prepared from normal sera. Moreover, rabbits immunized with the abnormal lipoproteins produced specific antibodies to this lipoprotein which reacted with a d < 1.006 lipoprotein in normal sera. All other lipoprotein fractions from normal sera were unreactive. It is not known whether this lipoprotein is abnormal by virtue of the presence of a unique peptide or because of secondary alterations in lipoprotein structure.