Abstract: It is possible to inactivate the early stage of lipid A synthesis of mucosal gram negative bacteria without compromising cell viability. In particular the lpxA gene in N. meningitidis was mutated and resulting lpxA knockout mutants were found to be completely lipopolysaccharide (LPS)-deficient. The major outer membrane proteins (OMPs) were detected in normal amounts. The finding provides important implications for understanding of structure and biogenesis of the outer membrane. On a practical level, the availability of LPS-deficient mutants of pathogenic mucosal bacteria such as N. meningitidis opens up new avenues to vaccine development. It enables easy isolation of endotoxin-free purified proteins, outer membranes or even whole-cell preparations for use in immunisation.