The aim of this study was to investigate the behavior of the protonated paralytic shellfish poisons saxitoxin (STX) and neosaxitoxin (NEO) in the gas-phase after ion activation using different tandem mass spectrometry techniques. STX and NEO belong to a group of neurotoxins produced by several strains of marine dinoflagellates. Their chemical structures are based on a tetrahydropurine skeleton to which a 5-membered ring is fused. STX and NEO only vary in their substituent at N-1, with STX carrying hydrogen and NEO having a hydroxyl group at this position. The collision-induced dissociation (CID) spectra exhibited an unusually rich variety and abundance of species due to the large number of functional groups within the small skeletal structures. Starting with triple-quadrupole CID spectra as templates, linked ion-trap MS n data were added to provide tentative dissociation schemes. Subsequent high-resolution FTICR experiments gave exact mass data for product ions formed via infrared multiphoton dissociation (IRMPD) from which elemental formulas were derived. Calculations of proton affinities of STX and NEO suggested that protonation took place at the guanidinium group in the pyrimidine ring for both molecules. Most of the observed parallel and consecutive fragmentations could be rationalized through neutral losses of H 2O, NH 3, CO, CO 2, CH 2O and different isocyanate, ketenimine and diimine species, many of which were similar for STX and NEO. Several exceptions, however, were noted and differences could be readily correlated with reactions involving NEO's additional hydroxyl group. A few interesting variations between CID and IRMPD spectra are also highlighted in this paper.