A combination of signals transmitted through the antigen receptor, membrane-bound cell interaction molecules and cytokine receptors induces B cell proliferation and differentiation into immunoglobulin-secreting or memory cells. It has recently been suggested by Turner et al.(Cell 1994. 77: 297) that the complex changes in gene activities accompanying high levels of immunoglobulin secretion are under the common control of a master regulator, Blimp-1 (B lymphocyte-induced maturation protein). We show here that in naive mouse B cells stimulated with lipopolysaccharide (LPS) alone (which leads to high IgM production), Blimp-1 is highly expressed, while cells co-stimulated with LPS and anti-μ F (ab′) 2 show low levels of Blimp-1 mRNA and no longer secrete Ig. Iγ1 sterile transcripts are, however, up-regulated after receptor co-ligation. Addition of interleukin (IL)-2 and IL-5 to LPS+ anti-μ F (ab′) 2-treated primary B cells led to up-regulation of Blimp-1 and IgM secretion. Transfection of a Blimp-1 expression vector also induced IgM secretion. The data indicate that Blimp-1 is an important regulator of immunoglobulin secretion by primary B cells, and suggest that its level of expression may determine the differentiation to Ig-secreting plasma cells or entrance and maintenance in the memory pool.