Gas-phase fragmentation patterns of poly(propylene imine) dendrimers DAB-dendr-(NH2)(n) with n = 4, 8, 16, 32, and 64 are described as a result of MSn electrospray ionization mass spectrometry (ESI-MS) studies. The generally accepted on-the-average globular shape of dendrimers is supported here by the linear relationship found between the extent of protonation and molecular mass (M-2/3). Unique fragmentation patterns are observed due to this globular shape. Most fragment ions are readily accounted for when, in addition to nucleophilic displacement reactions, proton shifts and rearrangements are taken into consideration. There is a striking difference in fragmentation behavior between singly charged dendrimers and multiply charged dendrimers. Therefore, it is proposed that the site of protonation within the dendritic framework has a large impact on the fragments observed. The position of the proton is largely dependent on both the relative proton affinities and the Coulomb repulsion between neighboring protonated sites. In case of singly charged dendrimers, electrostatic interactions are absent and the fragmentation is predominantly governed by the relative differences in proton affinity between the basic sites present in the dendrimer. In the gas phase the nitrogen atoms in the core of the dendrimer are the most basic ones present, leading to [M + H](+) ions carrying a protonated diaminobuthane core in all cases. This triggers a cascade of nucleophilic displacement reactions, starting with a bond cleavage of the central dendritic core and finishing with the formation of bis(1,1-propylamine)azetidinium (m/z 172) and fragments derived thereof. In the case of multiply charged dendrimers, Coulomb repulsions lead primarily to protonation of the peripheral tertiary amines, leading to the direct formation of bis(1,1-propylamine)azetidinium. These gas-phase reactions were subsequently utilized as a model for reactions in solution. The gas-phase reactions in ESI-MS thus provided a unique "fingerprint" area of dendrimer fragmentation adducts in the lower mit range (m/z < 180), which matches perfectly with that obtained from dendrimers after prolonged heating in aqueous solution.