The use of mutants of Salmonella typhimurium in which biosynthesis of specific lipopolysaccharide precursors is blocked has made possible both biosynthetic studies and structural analyses which provide the basis for the structure of the core polysaccharide shown in Fig. 6. The simplest mutant, which is unable to synthesize UDP-glucose, forms only the backbone structure, containing heptose, phosphate, and keto-deoxyoctonate. To this backbone are attached side chains containing glucose, galactose, and N-acetylglucosamine. The resulting core structure is found in the lipopolysaccharide of the rough strain, as well as in that of the GDP-mannose- deficient mutant. In the wild type organism, long O-antigenic chains composed of repeating units containing galactose, mannose, rhamnose, and abequose are linked to the core, perhaps to the N-acetylglucosamine residue, as indicated in Fig. 6. The rough phenotype could presumably arise from mutation either at the level of nucleotide sugar synthesis or at some stage in assembly or attachment of the O-antigenic side chains. The pathways of nucleotide sugar synthesis appear to be normal in most rough strains of S. typhimurium (42), a finding which suggests loss of a lipopolysaccharide transferase reaction in these mutants. The site of the enzymatic defect has not yet been established in these cases, but two distinct genetic types of rough mutants have been detected (18). It is interesting to speculate about the function of the lipopolysaccharide. The lipopolysaccharide can account for as much as 5 percent of the dry weight of the cell, and its synthesis clearly involves major expenditure both of energy and of material. Yet loss of the antigenic side chains, or even of a major part of the core structure, appears to have little or no effect on the ability of the organism to survive under laboratory conditions, since the rough and mutant strains grow as well as the wild type does. However, only the wild types, possessing the complete antigenic side chains, are pathogenic. It is possible that the lipopolysaccharide is an important factor in aiding the bacterium to evade host defense mechanisms, such as phagocytosis. Such a role is well established for the capsular polysaccharides of the pneumococci. No mutants have thus far been detected which lack the backbone or lipid portions of the lipopolysaccharide. It may be that these parts of the lipopolysaccharide play an essential role in the physiology of the organism