AbstractChromosomally distinguishable syngeneic mice were parabiosed and the resultant chimerism was followed for 6 weeks in the lymphoid organs, by culturing their cells with polyclonal mitogens, lipopolysaccharide (LPS) for B cells and phytohemagglutinin (PHA) for T cells. As expected of a recirculating population, the T cells equilibrated completely. The B cells in lymph nodes (LN) and Peyer's patches (PP) also equilibrated completely, suggesting that they too are recirculating. B cells in the spleen and blood, however, did not equilibrate over this period. After separation of parabiosed mice, the percentage of partner cells in both the recirculating T and B lymphocyte populations declined steadily, but it continued to rise in the LPS‐responsive populations in spleen and peripheral blood suggesting that they were derived from precursor populations which were themselves chimeric. Injection of lymphocytes into CBA/Ca or CBA/N mice showed that LPS‐responsive populations in LN and spleen localized differently.These results have been interpreted as demonstrating two major populations of LPS‐responsive B lymphocytes in the mouse, one recirculating and the other sessile. The recirculating population appears to be the only LPS‐responsive population in LN and PP. In the spleen, however, the recirculating cells constitute about a quarter of the LPS‐responsive cells, while the rest are sessile cells. The relationship between these two populations has yet to be clarified. CBA/N mice are deficient in both populations but the sessile one appears to be more severely