We examined the intracellular survival of Vi-capsulated (lipopolysaccharide; (LPS)-masked) and Vi-deleted (LPS-exposed) Salmonella typhi strains inside macrophage cell lines. Growth of LPS-exposed S. typhi was inhibited in both mouse and human macrophage cell lines. However, the LPS-exposed strain survived in a CD14-deficient mouse macrophage cell lines. Wild-type S. typhi strain, which expressed the Vi antigen and masked LPS, survived in the resting human macrophage cell line. When the Vi-capsulated S. typhi entered the cells, the production of tumor necrosis factor-α (TNF-α) was suppressed. In contrast, S. typhimurium and LPS-exposed S. typhi stimulated the macrophages to produce a high level of TNF-α.