It has been proposed that oxidative stress develops in tumors, with important consequences for growth and progression. To investigate this hypothesis, we measured low m.w. thiols, disulfides, protein-mixed disulfides and a pool of major anti-oxidant enzymes in renal-cortex as well as renal-cell carcinoma (RCC) specimens at stages I-II and III. Our data showed (i) a significant increase in the levels of total intracellular glutathione at both tumor stages (levels were 2.6-2.8 fold higher than those in the normal renal cortex), (ii) a marked lowering of the GSH/GSSG ratio in stage I-II accompanied by a significant decrease of many GSH-dependent enzymes (i.e., GPX, GST, GGT, GR) and (iii) unchanged GSH/GSSG ratio and GSH-dependent enzyme activity in stage III with respect to normal renal cortex. These results indicate that relevant variations exist in the glutathione antioxidant system in the different stages of RCC and support the hypothesis that oxidative stress plays an important role in RCC growth and progression.