Oxidative stress has been frequently implicated in the initiation and promotion phases of carcinogenesis. Antioxidant enzymes, which can antagonize this process, are lowered in a number of malignancies even though different findings have been reported in the literature. It has been shown that tumors have less copper/zinc superoxide dismutase (Cu/Zn SOD) in comparison with the more metabolically active tissues, but there is a large overlap between normal and tumor tissue. In order to examine the relationship between osteosarcoma at different degrees of proliferation and differentiation and Cu/Zn SOD levels, four different human ostosarcoma cell lines: HOS, U-2 OS, MG63, Saos-2 were studied for their production and release of Cu/Zn SOD. A normal human stromal cell line was used as control. Osteosarcoma cells were stimulated with TNF alpha, a cytokine previously shown to have antiproliferative activity. The release of Cu/Zn SOD into the supernatant was higher for the HOS and U-2 OS lines when compared to the other cell lines evaluated both in basal condition and after incubation with TNF alpha. Elevated intracellular levels of Cu/Zn SOD were shown except for the HOS and U-2 OS which possess high concentrations of the enzyme at 24 hours declining during the other incubation periods. These concentrations were increased after TNF alpha treatment. The different behaviour of the four cell lines evaluated might be explained by their degree of differentiation.