Solution folding of a protein removes major sections of it from their aqueous environment. Complete removal, by forming water-free gaseous protein ions with electrospray ionization/mass spectrometry, profoundly changes the conformation of cytochrome c. Of these ions＇ exchangeable hydrogen atoms, gaseous D2O replaces 30% to 70% in distinct values indicative of at least six conformational states. Although this is increased to >95% bp colliding ions with D2O, colliding instead with N-2 and subsequent D2O exposure gives the same H/D exchange values, although in different proportions; on solvent removal, denatured ions spontaneously refold. Deuterated Slate I, II, and V ions of a range of charge Values up to 17+ when charge stripped to 9+ ions do nor fold appreciably, even though their cross section decreases by 20%, confirming that each has a characteristic conformational structure insensitive to electrostatic repulsion; the charge solvation of an added protonated side chain also protects additional exchangeable sites. Dramatic temperature effects on H/D exchange also support unique State I,II, IV, and V conformers with a variety of charge values. Despite extensive H/D scrambling, dissociation to locate D sites of State I, II, N, and V ions indicates that four small alpha-helical regions are maintained even in the most open ionic conformations; these regions are consistent with salt bridge stabilization. In the more open conformers the alpha-helical regions could be partially converted to either beta-sheet or denatured structures. No close similarities were found between the gaseous conformer structures and those in solution, a cautionary note for the use of ESI/MS gas-phase data to characterize noncovalent interactions in solution.