Direct UV matrix-assisted laser desorption/ionization(MALDI) mass spectrometric analysis of uncomplexed,underivatized, highly sulfated oligosaccharides has beencarried out using ionic liquids as matrices. Under conventionally used MALDI time-of-flight experimental conditions, uncomplexed polysulfated oligosaccharides do notproduce any signal. We report that 1-methylimidazolium
-cyano-4-hydroxycinnamate and butylammonium 2,5-dihydroxybenzoate ionic liquid matrices allow the detection of picomole amounts of the sodium salts of adisaccharide, sucrose octasulfate, and an octasulfatedpentasaccharide, Arixtra. The experimental results indicate that both analytes undergo some degree of thermalfragmentation with a mass loss corresponding to cleavageof O-SO
3Na bonds in the matrix upon laser irradiation,reflecting lability of sulfo groups.