AbstractA general scheme for ionization and fragmentation of ions in Fourier‐transform ion cyclotron resonance mass spectrometry (FT‐ICRMS) is introduced. The technique is based upon excitation of high‐frequency (i.e. lowmass) primary ions (e.g. N +·2, Al+, H2O+·) which may be generated by standard ionization methods (e.g. electron ionization or laser desorption) inside the trap. Generation of the primary ions is followed by excitation of their cyclotron motion to high translational energy to serve as projectile ions. The projectiles serve two functions: to ionize neutral gas atoms and/or molecules (secondary ions) within the trap internal ion impact ionization (IIII), and to collisionally activate the secondary ions to induce fragmentation. Ionization by IIII is analogous to charge‐exchange ionization, in which a primary ion reacts with neutral analyte to produce ionization. When the projectile ions' cyclotron orbits are not excited (even for very long delay periods between ionization and detection), lower ion abundances are observed for the secondary ions derived from the neutral analyte(s), verifying that high energy ion impact must be responsible for the relatively high ion abundances observed when projectile cyclotron motion is excited: i.e., the mechanism of IIII is likely to be high‐energy charge exchange. Several advantages of the new technique include: accessibility of very high impact energy (keV) in FT‐ICRMS in both the laboratory and the center‐of‐mass frames of reference; ease in controlling the average energy transferred from projectiles to sample neutrals by moderation of the projectile ion's cyclotron radius; and the high ion‐molecule reaction rates attainable in FT‐ICR due to the long path length for trapped primary projectile ions at low pressure. Theory of ion formation and the problems associated with this technique (e.g. formation of secondary ions at different pre‐excitation