A Salmonella typhi conjugated vaccine was prepared by covalently linking the antigenic O-polysaccharide, selectively activated by periodate oxidation, to tetanus toxoid via reductive amination. The immunogenicity of the conjugate (O-TT) was examined by injecting Balb/c mice with 5 micrograms of the conjugate and Alhydrogel as adjuvant, boosting 14 and 28 days after the primary immunization, and quantification of the development of anti-polysaccharide and anti-tetanus toxoid antibodies by enzyme-linked immunosorbent assay. Mean anti-O-chain titres after the first and second boost were 129 and 502, respectively, while anti-tetanus toxoid titres were 159 and 1000, respectively. Anti-O-polysaccharide antibodies exhibited complement-mediated bactericidal activity against S. typhi. Immunized mice were fully protected against challenge with 10 LD50 of S. typhi Ty2 (p < 0.001) and partially protected against challenge with 100 LD50 of S. typhi Ty2 (p < 0.04).