Heat shock proteins (Hsps) represent dominant antigens in numerous microbial infections, suggesting a potential use of pathogen-derived Hsps for vaccination. The present study evaluates the immunogenicity and protective efficacy of groEL (Hsp60) of Salmonella enterica serovar Typhi against lethal challenge by S. Typhi Ty2 and Salmonella enterica serovar Typhimurium in mice. The groEL gene was cloned and expressed in Escherichia coli BL21 and purified by affinity chromatography. Immunization of mice with groEL resulted in a significant increase in antibody titers. Antibody isotyping revealed that groEL immunization induces both IgG1 and IgG2a antibodies. There was a significant increase in lymphocyte proliferation, interleukin-4 and interferon-gamma levels in cells isolated from immunized mice as compared to control. Immunization of mice with recombinant groEL protein with or without adjuvant conferred 70-90% protection against lethal infections either by S. Typhi Ty2 or S. Typhimurium. Passive immunization with anti-groEL sera also protected 50% mice against lethal infection.