Salts with low melting points, also termed room-temperature ionic liquids, can be used as matrices in matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). They have great vacuum stability, and can dissolve polar and apolar solutes including carbohydrates, biological oligomers and proteins. The ionic liquids give much more homogeneous sample solutions compared with solid matrices. We demonstrate the usefulness of using ionic matrices to determine the molecular weight of DNA oligomers by direct TOF mass spectrometric analysis. Three oligonucleotides were tested, (d(pT)10, d(pC)11, and d(pC)12), with several ionic matrices synthesized from different bases associated to two acids (3-hydroxypicolinic acid and 2,5-dihydroxybenzoic acid). The results obtained show that the best ionic matrices enhance the ion peak intensity of the oligonucleotides with respect to conventional molecular matrices under our experimental conditions. In one case, an ionic matrix provided a signal-to-noise ratio ten times higher than the corresponding molecular matrix. Several of the tested ionic matrices were liquids. However, all working ionic matrices were solids. Copyright © 2003 John Wiley & Sons, Ltd.