Hydrogen exchange results for cytochrome c and several other proteins show that they are composed of a number of foldon units which continually unfold and refold and account for some functional properties. Previous work showed that one Omega-loop foldon controls the rate of the structural switching and ligand exchange behavior of cytochrome c known as the alkaline transition. The present work tests the role of foldons in the alkaline transition equilibrium. We measured the effects of denaturant and 14 destabilizing mutations. The results show that the ligand exchange equilibrium is controlled by the stability of the same foldon unit implicated before. In addition, the results obtained confirm the epsilon-amino group of Lys79 and Lys73 as the alkaline replacement ligands and bear on the search for a triggering group.