Hydrgen/deuterium exchange reactions involving protonated triglycine and deuterated ammonia (ND3) have been examined in the gas phase using a Foumer transform ion cyclotron resonance (FT-ICR) mass spectrometer Ab intio and density functional theory (DFT) calculations have been carried out to model the exchanges and to obtain energetics and vibrational frequencies lot molecules involved in the proposed exchange mechanisms. Structural optimization and frequency calculations have been performed at the B3BLYP level of theory with the 6-31 1+G(d.p) basis set Transition states have been calculated at the same level or theory and basis set as above using the QST2 and QST3 methods. Single-point energy calculations have been NI formed at the MP2/6-311+G(d,p) level. Six labile sites of protonated triglycme were found to undergo H/D exchange Of these six labile hydrogens two are amide, three are ammonium. and one is carboxyl Detailed mechanisms for each or these transfers are proposed Qualitative onium ion and tautomer mechanisms lot the exchanges of ammonium and amide hydrogens, respectively, using semiempirical calculations were suggested in previous studies by Beauchamp et al As shown by the current ab initio and DFT calculations completed during this study. the mechanisms proposed in that study are notionally correct, however, the tautomer mechanisms ate shown here to be the result of the fact that a second stable isomer of protonated triglycine exists in which the amide I carbonyl oxygen is protonated. The exchange of the carboxyl hydrogen is found to proceed via a transition state resembling an ammonium ion interacting with a carboxylate moiety via two hydrogen bonds The current work thus provides significant mechanistic and structural detail for a considerably mole in-depth understanding or the processes involved in efts phase H/D exchange of peptides.