We demonstrate that the precolumn derivatization reaction, recently introduced by our laboratory for the selective labeling of carboxylated monosaccharides, cab be readily transposed to other glycoconjugates containing carboxylated sugar residues, namely sialogangliosides. The selective derivatization reaction described here involved the attachment of sulfanilic acid (a UV-absorbing tag) or 7-aminonaphthalene-1,3-disulfonic acid (a UV-absorbing and also fluorescing tag) to the sialic acid moiety of the gangliosides via the carboxylic group in the presence of water-soluble carbodiimide. This labeling of the sialic acid moiety of the gangliosides with a chromophore and/or fluorophore leads to the formation of an amide bond between the carboxylic group of the sugar residue and the amino group of the derivatizing agent, thus replacing the weak carboxylic acid group of the carbohydrate species by the stronger sulfonic acid group which is ionized over the entire pH range. Furthermore, novel electrolyte systems were introduced and evaluated for the separation of the derivatized and underivatized gangliosides. The addition of acetonitrile or α-cyclodextrin (α-CD) to the running electrolyte was necessary to break-up the aggregation of amphiphilic gangliosides and allowed for their efficient separation as monomers in aqueous media using capillary electrophoresis. Several operating parameters were investigated with these electrolyte systems including the additive concentration as well as the ionic strength, pH and nature of the running electrolyte. Acetonitrile at 50% (v/v) in 5 mM sodium phosphate at high and low pH or 15 mM α-CD in 100 mM sodium borate, pH 10.0, proved ideal, in terms of resolution and separation efficiency, for the group separation of mono-, di- and trisialogangliosides. On the other hand, the complete resolution of disialoganglioside isomers (e.g., GD1a and GD1b) necessitated the superimposition of a chromatographic component on the electrophoretic process. This was achieved by adding either a hydrophobic (e.g., decanoyl-N-methylglucamide-borate surfactant complex) or hydrophilic [e.g., poly(vinyl alcohol) or hydroxypropyl cellulose] selectors to the running electrolyte.