The effect of solvents was found to be critical for sample preparation in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). For proteins and oligonucleotides the use of 2-propanol/water as a solvent for different matrices can significantly improve the quality of spectra. This effect is demonstrated with proteins ranging in molecular weight from 12 to 150 kDa and with a special 19-mer oligonucleotide. A comparison of MALDI-MS using of 2-propanol as matrix solvent and high-performance capillary electrophoresis resulted in identical relative peak intensities for a p(dT)12-18 oligonucleotide mixture. Additionally, the effect of detergents for characterization of high molecular weight proteins in very dilute solutions was studied with this solvent. It was found that Triton X-100, up to a concentration of 1%, was highly compatible with MALDI measurements and even could improve the quality of spectra. Use of detergents for cell profiling has extended the detectable mass range to about m/z 75,000.