Spleen cells from mice preinjected with high doses of bacterial lipopolysaccharide did not generate anti-trinitrophenyl (TNP) plaque-forming cells in vitro to the T-dependent antigen, TNP-sheep erythrocytes, but did generate fully plaque-forming cells to the T-independent antigens, TNP-Ficoll and TNP-Brucella abortus. The immunological activity of B cells from such lipopolysaccharide-preinjected mice was analyzed in the present study. T cell-depleted spleen cells from mice injected with 30 micrograms of lipopolysaccharide 3 days previously did not respond to combined stimulation with TNP-sheep erythrocytes and concanavalin A-induced T cell-replacing factor and had no suppressive activity on normal T cell-depleted spleen cells. Splenic B cells, which were separated from T cells and macrophages from mice injected with 30 micrograms of lipopolysaccharide 3 days previously, responded only partially (about 25% of the control response) to combined stimulation with TNP-sheep erythrocytes and concanavalin A-induced cell-replacing factor in the presence of normal macrophages, but responded fully to TNP-B. abortus, regardless of the presence of normal macrophages. These results indicate that B cells responding to the T-dependent antigens are rendered unresponsive to antigenic stimulation in mice preinjected with lipopolysaccharide, whereas B cells responding to the T-independent antigens are kept intact.