The purpose of this study was to evaluate the efficacy of a vaccine consisting of the O-polysaccharide of the lipopolysaccharide (LPS) of Francisella tularensis chemically conjugated to bovine serum albumin. The results show that conjugation preserved both the antigenicity and immunogenicity of the polysaccharide moiety. Mice vaccinated with the glyco-conjugate, but not with BSA alone, were completely protected against an intradermal challenge with a highly virulent type B strain of F. tularensis, and partially protected against an aerosol challenge with the same strain. However, such vaccination failed to protect against an aerosol challenge with a virulent type A strain of the pathogen. The results suggest that the O-antigen of F. tularensis could be considered as a potential component of a subunit vaccine against type B, but not type A strains of F. tularensis.