Abstract Background Lipopolysaccharide (LPS), or endotoxin, is considered responsible for the pattern of cytokine activation and the subsequent pathophysiological events during Gram-negative septic shock. To determine whether non-LPS components of Neisseria meningitidis are able to induce cytokine activation, the cytokine-inducing capacities of serogroup B wild-type N. meningitidis H44/76, of an LPS-deficient mutant (Plak 33) and of meningococcal LPS in human peripheral blood mononuclear cells were studied. Methods 2-Keto-3-deoxyoctanate spectrophotometry was used to obtain a molar-based quantitative comparison between LPS and bacteria. Results Whole meningococci H44/76 were more potent inducers of cytokine production than isolated LPS; the LPS-deficient meningococci, Plak 33, were also able to induce cytokine production. LPS-deficient meningococci supplemented with an amount of LPS equivalent to that present in the wild-type strain produced the same amount of cytokines as the wild-type meningococcus. Conclusion LPS is not the sole toxic element in meningococcal sepsis, because non-LPS components of N. meningitidis are able to induce cytokine activation substantially. Antiendotoxin therapy alone may not be sufficient to inhibit the pattern of cytokine activation and the subsequent pathophysiological events during meningococcal septic shock.