The Vi capsular polysaccharide of Salmonella typhi is a linear homopolymer of poly-alpha(1----4)GalNAcp variably O acetylated at the C-3 position. Serum antibodies elicited by this antigen confer protective immunity against typhoid fever. The relation between the immunologic properties and structure of Vi was investigated by carboxyl reduction, O deacetylation, and acid hydrolysis. The immunogenicity of Vi was closely related to its degree of O acetylation. Partial O deacetylation slightly increased immunogenicity; complete O deacetylation eliminated the immunogenicity of Vi. O-deacetylated Vi, however, still reacted with antisera prepared by injection of whole bacteria. Carboxyl reduction, in contrast, had a comparatively slight effect upon both the immunogenicity and antigenicity of Vi. Retention levels of antigenicity after acid treatment were greater for both the native and carboxyl-reduced Vi than for the O-deacetylated product. The Courtauld-Koltun space-filling model of a pentamer of Vi demonstrated that the bulky nonpolar O-acetyls, which protrude in rows on both sides, make up most of the surface. The carboxyls are less exposed and are partially shielded by the O-acetyls. The molecular model thus provides an explantation for the dominant role of the O-acetyls, as well as the lesser effect of carboxyl reduction, upon the immunologic properties of Vi.