As with other pathogens whose surface polysaccharide is an essential virulence factor and a protective antigen, there is an inverse relation between the age incidence of shigellosis and the presence of serum IgG LPS antibodies. Also, a critical level of serum IgG anti-LPS correlates with resistance to shigellosis in young adults. On the basis of these findings, we are evaluating Shigella conjugates designed to induce IgG anti-LPS in children in order to prevent shigellosis. Conjugates of the O-specific polysaccharides of S. sonnei and S. flexneri type 2a bound to recombinant P. aeruginosa exoprotein A (rEPA) and hepatitis B vaccine (control) were administered on a random basis to healthy 4-6 year old children at 0 and 6 weeks. Blood was withdrawn before the first and second injections and at 4 and about 24 weeks after the second injection. Liver function assays and the serum IgM, IgA and IgG composition of anti-LPS(ELISA) were measured in each serum. One hundred and forty seven subjects received one of the above vaccines; the proportion of dropout was 10%. Minimal local reactions were reported by 5% and none of the children had fever or abnormal laboratory results. The first injection of S. flexneri type 2a conjugate elicited a statistically significant rise: the preinjection IgG anti-LPS geometric mean (GM) was 1.7 and the postinjection was 21.6. The S. sonnei also elicited a statistically significant rise: the IgG anti-LPS GM rose from 0.3 to 13.2. Recipients of hepatitis B vaccine had no change in their anti-LPS antibodies and there was no rise in the heterologous LPS antibodies of the vaccinees. Injection of the two Shigella conjugates was safe and immunogenic in children. The effect of the second injection and the duration of the conjugate induced anti-LPS antibodies are under study.