Hydrogen/deuterium (HID) exchange reactions between different elongated conformations of [M + 11H](11+) ions of ubiquitin and D2O are studied by a combination of ion mobility spectrometry (IMS) and mass spectrometry techniques. Three conformers (B, C, and D), resolved in the IMS separation, each exchange similar to 27 hydrogens upon exposure to 0.06 Torr of D2O vapor for similar to 35 to 40 ms. However, a region of the IMS spectrum that appears between the C and D states (corresponding to ions that undergo a structural transition during the mobility separation) undergoes substantially more exchanges (similar to 39 total sites, 44% more than the B, C, and D states). Selection and activation of the individual B, C, and D states reveals that the increased HID exchange occurs during the transition between structures. Overall, these studies suggest a key process in establishing the maximum exchange levels involves structural transitions, which allow protected sites to be exposed for some fraction of the reaction time. Analysis of changes in exchange levels upon structural transitions can provide insight about common regions of structure that exist in the B, C, and D conformations.