The structures of 4 tryptic peptides are studied using matrix-assisted laser desorption ionization-ion mobility mass spectrometry, circular dichroism spectroscopy, and solution-phase hydrogen-deuterium exchange mass spectrometry. The sequences LLGNVLVVVLAR (bovine hemoglobin) and HGTVVLTALGGILK (horse heart myoglobin) are helical within their native proteins and as gas-phase ions [J. Am. Chem. Soc. 2002, 124, 4214]; however, the two peptides undergo very different structural transitions as their local environment is changed. For example, circular dichroism measurements suggest that the peptide LLGNVLVVVLAR assumes a beta-hairpin conformation in aqueous/methanolic solvent systems; however, the helical structure of HGTVVLTALGGILK appears to be denatured (takes on a random coil conformation) upon cleavage from the protein. The gas-phase structure of the peptides exhibit a high correlation to the conformation observed by circular dichroism in 2,2,2-trifluoroethanol, suggesting that the gas-phase structure may be utilized for solution-phase relevant studies of peptide folding.