Wild-type and cell wall mutants of Salmonella were examined for sensitivity to ingestion and intracellular killing in vitro by mouse peritoneal macrophages and guinea pig polymorphonuclear leukocytes. A complete polysaccharide core of the cell wall is important for resisting ingestion and intracellular killing, and the presence of the O-specific side chains contributes further resistance. Uridine diphosphate-gal-4-epimeraseless mutants grown on galactose-supplemented medium, rendering them smooth phenotypes, showed resistance to ingestion and intracellular killing similar to the wild type.