The reactivity of cystine toward electronically excited singlet O-2 (a(1)Delta(g)) has been long debated, despite the fact that most organic disulfides are susceptible to oxidation by singlet O-2. We report a combined experimental and computational study on reactions of singlet O-2 with gas-phase cystine at different ionization and hydration states, aimed to determine reaction outcomes, mechanisms, and potential energy surfaces (PESs). Ion-molecule collisions of protonated and dideprotonated cystine ions with singlet O-2, in both the absence and the presence of a water ligand, were measured over a center-of-mass collision energy (E-col) range from 0.1 to 1.0 eV, using a guided-ion-beam scattering tandem mass spectrometer. No oxidation was observed for these reactant ions except collision-induced dissociation at high energies. Guided by density functional theory (DFT)-calculated PESs, reaction coordinates were established to unravel the origin of the nonreactivity of cystine ions toward singlet O-2. To account for mixed open- and closed-shell characters, singlet O-2 and critical structures along reaction coordinates were evaluated using broken-symmetry, open-shell DFT with spin contamination errors removed by an approximate spin-projection method. It was found that collision of protonated cystine with singlet O-2 follows a repulsive potential surface and possesses no chemically significant interaction and that collision-induced dissociation of protonated cystine is dominated by loss of water and CO. Collision of di-deprotonated cystine with singlet O-2, on the other hand, forms a shortlived electrostatically bonded precursor complex at low E-col. The latter may evolve to a covalently bonded persulfoxide, but the conversion is blocked by an activation barrier lying 0.39 eV above reactants. At high E-col, C-S bond cleavage dominates the collision-induced dissociation of di-deprotonated cystine, leading to charge-separated fragmentation. Cross section for the ensuing fragment ion H2NCH(CO2-)CH2SS center dot was measured as a function of E-col, and the mechanism of charge-separated fragmentation was discussed. It was also found that the reaction of deprotonated cystine with singlet O-2 follows a similar mechanism as that of di-deprotonated cystine, but with an even higher activation barrier (0.72 eV).