The aim of the present study was to analyze the effect of LPS on the localization and differentiation of splenic B lymphocytes. Therefore, we used a double immunoperoxidase technique which enabled us to detect both the IgM+ IgD- marginal zone lymphocytes and the IgM+ IgD+ follicular lymphocytes in the same tissue section. Next to a dramatic disappearance of the predominantly IgM+ IgD- lymphocytes in the marginal zone shortly after an intravenous injection of LPS, an increased number of these cells could be found in the splenic follicles. The present results strongly suggest that the IgM+ IgD- cells in the splenic follicles represent immigrating marginal zone lymphocytes, and not differentiating follicular B cells, because no IgM+ IgD- cells could be observed in the follicles of draining lymph nodes shortly after a subcutaneous injection of a similar amount of LPS. These observations support the suggestion that LPS induces a migration of marginal zone lymphocytes into the follicles. The present results also showed the formation of IgD plasmablasts in the inner PALS and around the terminal arterioles of the spleen after LPS administration. The induction of IgD plasmablasts appeared to be a specific effect of LPS which may be related to its toxic properties.