The predominant accumulating cells in the lymphoid tissue of MRL/lpr mice have been shown to carry the B220 cell marker. This antigen is expressed on B cells and on T-cell precursors. In order to know the pathogenic involvement of cells carrying this marker, we treated MRL/lpr mice periodically with RA3-6B2, a specific anti-B220 monoclonal antibody, or rat IgG2b as a control. After 12 weeks of treatment, a significant reduction (P less than 0.01) in the size of the lymph nodes and spleen was observed only in the group treated with RA3-6B2 monoclonal antibody. This reduction was mainly due to a decrease in the Thy-1.2+ and B220+ subpopulations. Anti-DNA and anti-Sm antibody titres were also reduced significantly (P less than 0.01) after the therapy. Proliferative response to mitogens (Con A, PHA, LPS) and IL-2 production was not improved after the anti-B220 treatment. These results suggest a pathogenic role of lymphocytes carrying the B220 marker in the autoimmune disease of MRL/lpr mice.