Preparation is described of the surface of the first monoisotopic cationic (109)Ag nanoparticles (AgNPs), covering commercial and modified MALDI targets, along with examples of the use in MS analyses of various low-molecular-weight (LMW) organic compounds, including alkaloids, saccharides, amino acids, nucleosides, nucleic bases, and other organics. The new targets, compared to those covered by naturally occurring silver, allow analyte detection with higher sensitivity, mass accuracy, and resolution. Moreover, monoisotopic triatomic silver cations (109)Ag(3)(+) appear to be applicable for analyte cationization.