Lipopolysaccharide (LPS) was extracted from six species of Bacteroides by the phenol/water, petroleum/chloroform/ phenol, and Triton/magnesium methods. Yields and chemical analysis demonstrated that the products were different. Biological activity (endotoxicity) was assessed by the limulus amebocyte lysate (LAL) assay, induction of tumor necrosis factor (TNF) from human mononuclear leukocytes, and a lethality model with galactosamine-sensitized mice. Results showed that endotoxicity varied greatly depending on the species and the extraction method. LPS prepared by the phenol/water method was most endotoxic and that from Bacteroides fragilis had the greatest activity. Compared with Escherichia coli LPS, the phenol/water extract of B. fragilis was sevenfold more active in the LAL assay and marginally less active (five-to seven-fold) in the bioassay for TNF induction. However, when B. fragilis LPS was added to E. coli LPS, the induction of TNF was inhibited. In the mouse model, B. fragilis LPS was 5,000-fold less toxic. If the gastrointestinal tract is the source of the endotoxin in patients with systemic inflammatory response syndrome, then the obligately anaerobic Bacteroides species, which outnumber the facultative species such as E. coli by 1,000-fold, should not be overlooked.