Gangliosides, sialic acid(s)-containing glycosphingolipids, were separated by capillary zone electrophoresis and detected with either UV or electrospray mass spectrometry. Several electrolyte systems were evaluated for the separation of underivatized gangliosides. The best result was obtained by using 50 mM borate and 50 mM phosphate buffer containing 20 mM alpha-cyclodextrin at pH 9.9. The four major ganglioside forms (GM1, GD1a, GT1b, GT1b) were successfully separated, and, moreover, each ganglioside yielded two peaks, splitting by the difference in chain length of the ceramide moiety. The resolution obtained in CE-UV could not be reproduced in CE-MS because of the incompatibility of the borate/phosphate buffer to ESI-MS. With the use of more volatile buffers, such as ammonium acetate or 2-[N-cyclohexylamino]-ethanesulfonic acid, baseline resolution was obtained for gangliosides having different number of sugars, but the two disialoganglioside isomers, GD1a and GD1b, were coeluted. (C) 1997 Elsevier Science B.V.