In this work, we employ semiempirical and low-level ab initio molecular orbital theories with isodesmic/isogyric reactions to estimate the energetics of free radical reactions important to radiolytic damage to DNA. Results are presented (1) for H . and OH . addition reactions to the natural DNA bases, (2) for the addition of H . to the DNA base radical adducts so obtained, and (3) for the dehydration of the DNA base hydrates and regeneration of the undamaged bases. The technique employed sums the calculated enthalpy of an isodesmic reaction with the experimentally known reaction enthalpy of an associated reaction to estimate the enthalpies of the DNA base reactions of interest. The calculational techniques employed are the ROHF/6-31G* ab initio method and the ROHF/PM3 semiempirical method. For H . addition reactions, the ROHF ab initio method employing the 6-31G* basis set gives results that are in closest agreement with known experimental results. For the OH . addition processes, the ROHF/PM3 semiempirical technique results in predictions more in keeping with the experimental model systems. The values calculated are employed to estimate the heats of formation of various DNA base radicals and DNA base hydrates. Economical PM3 calculations of isodesmic reactions when combined with well-known experimental enthalpies of reaction are found to yield reliable thermodynamic quantities.