GroEL is a heat shock protein, involved in the folding of denatured proteins under stressed conditions. Flagellin is a structured protein of flagella, and can undergo phase variation so that at any one time, synthesis of flagellin occurs from either of two genes, fliC or fliB. Porins, of which OmpC is an example, allow passage of nutrients and small molecules through the bacterial cell outer membrane. All of these proteins have previously been described as being immunogenic. In the work described here, antibodies specific to each of these antigens were detected in both innately susceptible and resistant mice after infection with an attenuated strain of S. typhimurium, and after subsequent challenge with the virulent organism, suggesting that they may each be involved in protective immunity. The immunogenicity of a vaccine consisting of these four recombinant Salmonella antigens was assessed in the mouse model. GroEL- and flagellin-specific antibodies were detected in innately susceptible mice after immunisation together with the adjuvant DDA. Moreover, analysis of IgG isotypes showed increased titres of both IgG1 and IgG2a, the latter indicating that cell-mediated immunity had been generated. However, challenge of immunised mice with virulent S. typhimurium demonstrated that the protective efficacy of the vaccine was of only low-level. Immunisation of innately susceptible and resistant mice using a tetravalent DNA vaccine expressing all four antigens resulted in increased antibody against GroEL, FliC and FlijB in both mouse strains. As with the subunit vaccine, IgG isotype analysis showed increased titres of both IgG1 and IgG2 indicting that both Type 2 and Type 1 helper T-cell responses had been elicited. However, considerable variation was observed within immunised mouse groups and so the protective efficacy of the vaccine was not determined.