Glutathione (GSH) was examined with respect to its ability to protect DNA against1O2damage. We have found that GSH protected, at least partly, the DNA against inactivation by1O2. Up to 10 mM the protection increased as a function of GSH concentration. Above 10 mM the protection remained constant and less than expected on the basis of scavenging/quenching of1O2, in contrast to the protection offered by sodium-azide. Especially at the higher concentrations of GSH the protection against the biological inactivation is accompanied by an increase in single-strand breaks and also probably lethal base damage. However, all together the data suggest that at least in the physiologically important range (0.1–10 mM) GSH is able to protect efficiently against1O2-induced inactivating DNA damage.