Adhesion to and penetration of HeLa cell monolayers by Salmonella typhi Ty2 requires the presence of a complete lipopolysaccharide as demonstrated by the inability of polysaccharide-defective mutants to invade the monolayer. Lysis of HeLa cell monolayers by Salmonella typhi Ty2 is associated with intracellular bacterial multiplication and no detectable production of extracellular toxins. The ability of Salmonella typhi to invade and lyse monolayers could provide a novel system for the study of its ability to invade the bloodstream from the intestine.