Selective binding of crown ethers to model protonated peptides is utilized to study the site selectivity and mechanisms of gas-phase hydrogen/deuterium exchange reactions with ND3 in an external ion source FT-ICR mass spectrometer. Mechanisms for H/D exchange reactions in the gas phase can be classified into two different types: Type I involving direct participation of the labile protons at the charge site and Type II in which the charge site at most plays only an ancillary role in the process (e.g., salt bridge formation). Localization of the labile proton at the charge site by crown ether attachment inhibits Type I processes, as evidenced by a dramatic reduction in the rates of H/D exchange. For example, crown ether attachment to protonated ethylenediamine and 1,4-diaminobutane inhibits H/D exchange reactions, while the free protonated species undergo rapid exchange of all five labile hydrogens. Type II processes are still observed with the crown ether adducts. Both the amide and the carboxyl hydrogens of peptides exchange via a Type II process for which a salt bridge mechanism has been proposed. In the salt bridge mechanism, the charge site may play an important role by stabilizing a charge separated ion pair. Immobilization of the labile proton by crown ether attachment does not eliminate this stabilization. Charge localization by crown ether attachment also affects the dissociation processes of protonated peptides, inhibiting charge directed mechanisms where endothermic proton transfer from the most basic group to a less basic site is a prerequisite for fragmentation. Collisional activation of the crown ether complex with protonated GGDPG and GGI results in no backbone cleavage in the peptide, while the free protonated peptides lead to cleavage at the C-terminus side of aspartic acid and the second glycine, respectively.