A heterologous antiserum (antiserum 7420) against B-lymphocyte antigen(s) was raised in a rabbit by immunization with peripheral blood lymphocytes from a patient with chronic lymphocytic leukaemia (CLL). After absorptions with pooled normal human serum, IgA, IgD, and IgM M-components, the fluorescein isothiocyanate-conjugated F(ab')2 fragments were prepared and further absorbed with normal peripheral blood leucocytes. The F(ab')2 fragments, studied in direct immunofluorescence, reacted with both normal and CLL B lymphocytes but not with T lymphocytes. Comparative studies with an HLA-DR antiserum showed that the antigen(s) detected by 7420 antiserum did not redistribute together with HLA-DR antigens in cocapping experiments, nor did the HLA-DR antiserum block the reaction of 7420 F(ab')2 fragments with B lymphocytes. The 7420 F(ab')2 fragments prcipitated detergent-solubilized B-cell membrane material with a molecular weight of around 40,000 and 150,000 daltons. The conclusion drawn is that the 7420 and HLA-DR antigens are different. The 7420 antigen was also shown to be different from classical HLA antigens, beta 2-microglobulin, surface immunoglobulin, the Fc receptor, and HC protein.