The frequency of murine B lymphocytes that respond to antibodies directed against membrane IgM was measured. These anti-mu antibodies induced all, or almost all, resting B cells to enlarge over the first 24 h of stimulation. This probably represents the transition from the resting state (G0) to active transit through the cell cycle. In contrast, only a fraction of these cells, approximately 60% for BDF1 mice, continued through the cell cycle into S phase. This is consistent with previous experiments that had suggested there were some types of B cells that did not proliferate in response to anti-mu. The results presented here demonstrate that many, perhaps all, of these nonresponding B cells, both from normal mice and from mice with the xid defect, actually do respond to the presence of anti-mu by going through early parts of the cell cycle. These cells appear to become blocked at some point before the beginning of S phase, perhaps requiring a signal from a T cell or a macrophage to continue through the cell cycle. Thus, the role of antigen may be to prepare all B cells for proliferation. Different subpopulations of B cells may then require different regulatory signals before actually proliferating or before differentiating into antibody-secreting cells.