Autoimmune-prone NZB±NZW FI (B/W FI) mice produce a high titer of anti-DNA antibodies.In vivoandin virrostudies showed that in the early life of these mice, the immunoglobulin isotype of these antibodies almost exclusively belongs to IgM class, however, IgG anti-DNA antibodies begin to develop when the mice are about 5–6 months old and the titer exceeds that of IgM antibodies from age 7 months on. We asked whether or not the B cell population responsible for IgM and IgG antibody production belongs to the same lineage. The surface phenotypes of B cell populations responsible for the spontaneous production of either IgM or IgG anti-DNA antibodies were examined using panning and sorting methods with several monoclonal antibodies to B cells, including CD5 (Ly-I) and Lp-3: the latter defines a unique B cell differentiation antigen. We obtained evidence that surface phenotypes of B cells secreting IgM anti-DNA antibodies belong to CD5+Lp-3−- and those of B cells secreting IgG anti-DNA antibodies which occur only in old B/W FI mice belong to CD5−- Lp-3+subpopulations. The majority of peritoneal B cells were CD5+Lp-3+throughout the life span of the mice and anti-DNA antibody production was never evidenced. These findings were discussed in relation to age-associated changes of B cell populations in the spleen of this strain of mice.