Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry of oligosaccharides and gangliosides normally causes loss of sialic acid, particularly when alpha-cyano-4-hydroxycinnamic acid is used as the matrix. In addition, the potential signal is split because both positive and, to a greater extent, negative ions are formed while signals are frequently complicated as the result of partial alkali-salt formation. In order to stabilize the sialic acid moieties under MALDI conditions and to divert all of the signal into the positive-ion mode, a method involving their conversion into methyl esters has been developed. The method is relatively rapid and produces strong positive-ion signals from N-linked oligosaccharides containing sialic acid and from gangliosides. The latter compounds are stable, even in the presence of alpha-cyano-4-hydroxycinnamic acid. They give abundant molecular (MNa+) ions, but with sufficient residual in-source fragmentation to allow the sequence of the sugar chain to be determined. The sialic acid residue is stable after methylation, irrespective of its linkage to the parent molecule.