Lipooligosaccharde (LOS) is one of the major surface antigens of Neisseria meningitidis and nontypable Haemophilus influenzae. We are investigating detoxified-LOS protein conjugates from N. meningitidis and nontypable H. influnzae. 500 mg to 1 g of purified LOS s were prepared from N. meningitidis strain 78800(L10) and three LOS-type strains of nontypable H. influenzae. These LOSs have no human glycolipid-like lacto-N-neotetraose structure. A 10,000-fold detoxification of the LOSs as measured by LAL assay has been achieved by treating them under anhydrous conditions with hydrazine. These detoxified LOSs will be conjugated to carrier proteins such as tetanus toxoid and meningococcal outer-membrane proteins by the method we have developed (Infect. Immun. 61:1873-1880, 1993). The immunogenicity of these conjugates will be evaluated in animal models.