Immunoadsorbents consisting of rabbit anti-DR antibodies bound to Staphylococcus aureus were used to bind DR antigens from NP40 cellular extracts of cultured B lymphoid cells. When injected into rabbits, these DR antibody absorbents elicited the production of antibodies that were shown by both serologic and immunochemical techniques to react specifically with the DR antigen molecule. A rosette inhibition assay with B lymphoid cells and anti-DR xenoantisera was used to detect DR antigens in human serum. DR serum antigens could be found in an enriched preparation of serum lipoproteins obtained by centrifugation in KBr. In addition, sera from some patients with neoplastic diseases contained higher levels of DR serum antigens than those found in normal individuals.