Sialic acids, comprising a group of N- and O-acyl as well as O-methyl and O-sulfate derivatives of neuraminic acid, are differently linked to various sugars of glycoproteins and gangliosides. Thus, the great molecular variety already existing in the asialo-portion of glycoconjugates is much increased by the addition of sialic acids. This structural diversity may be mirrored by a high antigenic diversity of the oligosaccharide part of complex carbohydrates. However, not much is known of such an influence of the sialic acid moieties of glycane chains, although antibodies against many non-sialylated oligosaccharides are known. In most cases investigated so far, sialic acids reduce or even prevent antigenicity of oligosaccharide chains and of the protein or lipid parts of glycoconjugate molecules, respectively. Enzymic removal of sialic acid or reduction of its carboxylic group to an alcohol residue alters or significantly increases the antigenicity. In contrast to this masking effect, sialic acids have been found to act as antigenic determinants. N-Acetylneuraminic acid in different linkages to other sugars is an essential component of various antigens in human erythrocytes, and N-glycolylneuraminic acid determines the blood group specificity of East-Asian dogs. The latter sialic acid also plays a role in immunological processes in man. N-Glycolylneuraminic acid probably cannot be synthesized in man, but is derived from the foodstuffs and incorporated into tissue glycoconjugates in small quantities. Sialic acid O-acetyl groups are also involved in immunological processes by modifying the antigenicity of glycoproteins and polysaccharides or by contributing to the specificity of tumor antigens. Evidence for a role of the multiple forms of sialic acids as differentiation antigens is accumulating.