We have previously reported that chronic exposure of rats to cigarette smoke inhibits the antibody-forming cell (AFC) response to both T-dependent and T-independent antigens and may reflect B cell dysfunction. In this communication we extend these studies to show that T cell functions are normal in chronically smoke-exposed rats (SM) as judged by their responses to mitogens and "nominal" or alloantigens. While B cells from SM respond significantly to the B cell mitogen lipopolysaccharide (LPS), they fail to proliferate in response to anti-IgM (anti-mu) or to produce significant AFC response to sheep red blood cells. On the basis of the number of rosettes formed with trinitrophenylated (TNP) horse red blood cells; the frequency of TNP-binding cells (TNP-ABC) in the spleens of SM is comparable to sham control rats. However, the proliferation of TNP-ABC to TNP-Brucella abortus is significantly decreased in SM. These differences in SM B cell responses, i.e., between LPS and anti-mu/antigen, may to be related to the ability of LPS to bypass a portion of the membrane signal transduction cascade. These results suggest that cigarette smoke affects an early step(s) in the antigen-dependent B cell signal transduction pathway.