The ionization energies of two thiol model compounds (methyl mercaptan and cysteamine) are calculated at the ROHF/6-31G* level to aid our understanding of the mechanisms involved in DNA radioprotection. Methyl mercaptan, the thiolate anion, and its trihydrated form are fully geometry optimized. The resulting gas-phase Koopmans ionization energies are 9.68, 1.67, and 3.63 eV, respectively. The ionization energy for the solvated methylthiolate anion, CH3S-(aq), calculated through the use of the SCRF model (epsilon = 78), the Born charge term, and a discrete hydration shell, leads to a Koopmans value of 5.6 eV. This result is in good agreement with the corrected vertical solution-phase ionization energy calculated by using the same model (5.4 eV) and with experiment (5.7 +/- 0.2 eV). The gas-phase ionization energies of cysteamine, its cation, zwitterion, and the pentahydrated form of the latter are reported. We find the Koopmans ionization energy of the anti configuration of the zwitterion to be ca. 6.0 eV. Discrete hydration of the negatively charged sulfur increases the ionization energy by ca. 0.55 eV per water while hydration of the amine group decreases it by ca. 0.1 eV per water. Subjecting the pentahydrated zwitterion to the SCRF model leads to a Koopmans solution-ionization energy of 6.42 eV. These results predict that bath the aqueous thiolate anion and the aqueous cysteamine zwitterion will reduce radiation-induced DNA base cation radicals via direct electron transfer as found experimentally. On the basis of energetics of the solvent-solute interactions, we propose that the electron transfer process between the cysteamine zwitterion and DNA cations will be influenced by the intervening solvent and suggest that displacement of the primary solvation layer upon ion pair formation will decrease the zwitterion’s ionization energy, thereby facilitating the electron transfer.