Cigarette smoke contains detectable amounts of cyanide, regardless of the type of cigarette. The very high levels of this compound in plasma of amblyopic smokers suggests that cyanide causes optic neuropathy. The detoxification of cyanide in man occurs through various metabolic pathway; the most important are those that use sulfur to transform cyanide into thiocyanate. One of the richest sources of reduced sulfhydryl groups is reduced glutathione (GSH). For this reason we investigated red cell GSH levels in non-smokers, in healthy smokers and in smokers affected by optic neuropathy to ascertain whether this compound is a marker of the disease. Red cell GSH levels in the non-smokers group were similar to those of affected smokers. On the contrary, GSH levels in healthy smokers were significantly more elevated. During therapy with vitamin E we noted that the concentration of GSH decreased with the progression of the disease and increased with recovery. Moreover, there was a good correlation between GSH levels and clinical findings. Our findings demonstrate that GSH plays a key role in the detoxification of cyanide and so it could be a marker of tobacco smoke-induced optic neuropathy.