Lipopolysaccharides (LPSs) from anaerobic gram-negative bacteria, including those of low endotoxic activity that are isolated from Bacteroides, Prevotella, and Porphyromonas are potent inducers of DNA replication and polyclonal immunoglobulin production in murine B lymphocytes. The activation is dose-dependent and T cell-independent. Replication of DNA and production of immunoglobulins were also stimulated by lipid A and by the LPS heteropolysaccharide that were isolated by mild acid hydrolysis of the LPSs of Bacteroides fragilis and Fusobacterium nucleatum. Combinations of LPS, lipid A, and acid-degraded polysaccharide amplified the blastogenic response. Antibodies that react with the polysaccharide part of LPSs isolated from members of the Bacteroidaceae are present in healthy human serum.