For nucleic acid and peptide analytes as well as other molecules, which carry both positively and negatively charged groups, detection of positive and negative ions under the same desorption and ionization conditions is usually possible. In some reports, similar yields/peak intensities for positive and negative ions were observed. Models have been proposed to explain the observations. For example, the energy transfer induced disproportionation assumes that in the solid sample, two analyte molecules share an active proton through hydrogen bonding. A closely located excited matrix molecule transfers its energy to the analyte dimer to induce disproportionation, which generates one protonated analyte molecule and one deprotonated analyte ion. In the context of the ion pair thermal model, where free ions in the plume are not considered a requirement for ion detection, and ion pairs with sufficient energy are mainly responsible for ion detection, these observations can be easily explained. In the plume, both types of ion pairs with analyte being positive ions and those with analytes being negative ions exist, and in some cases with close to equal quantity. Their energies are about the same, and thus the chance for their separation by ion extraction potential to become detectable free ions is about the same. Therefore, the detection of positive and negative analyte ions under the same desorption and ionization is observed.