Glutathione (GSH) is one of several intracellular hydrogen donating species thought to compete with O2, a damaging species, to repair radiation induced free radical damage. The O2 K factor was determined for normal Chinese hamster V79 cells, V79 cells made acutely thiol deficient (no detectable GSH or NPSH) using the gamma-glutamyl-cysteine synthetase enzyme inhibitor D,L-Buthionine-S,R-sulfoximine (D,L-BSO), or a human skin fibroblast cell line GM3877 which, because of the nature of its genetic defect, has chronically low levels of GSH (7% of normal skin fibroblasts). The K factors for normal V79 cells, treated with BSO or GSH deficient human fibroblasts, were 0.54, 0.15, and 0.1% O2, respectively. While thiol depletion affects the O2 K factor, V79 cells without any detectable GSH were still not as sensitive as the genetically deficient line GM3877 with 7% of normal GSH values. Other factors which may influence the results are whether the GSH levels remain low or regenerate following irradiation and the intracellular distribution of GSH.