The thermal unfolding of unsolvated cytochrome c has been examined in the gas phase using ion-mobility measurements. Measurements were performed for the +5, +6, and +7 protonated charge states from around room temperature up to 573 K. The (M + 5H)(5+) charge state remains folded at 573 K while (M + 6H)(6+) and (M + 7H)(7+) go through a series of unfolding transitions as the temperature is raised. Molecular dynamics simulations were performed using the CHARMM force field. The simulations an in qualitative agreement with the experimental results: the +7 charge states unfold as the temperature is raised and the +5 charge states remain compact. Addition of two protons to the +5 charge state flattens the energy landscape so that the folded and unfolded conformations have similar energies. Entropy presumably drives the unfolding of the +7 charge state as the temperature is raised.