The cytosolic form of selenium-dependent glutathione peroxidase detoxifies both hydrogen and lipid peroxides and therefore represents a major component of the cellular anti-oxidant defenses. In order to study the biological role of this enzyme, we generated an expression construct in a retroviral vector, which when introduced into immortalized human T-cells, resulted in significant increases in the activity of this important enzyme. This effect is stable over extended maintenance in culture. The anti-oxidant defenses in these same cells are also shown to be attenuated by chemically reducing cellular glutathione levels. Collectively, the ability to both increase and decrease the anti-oxidant defenses in human T cells results in a useful model system for the study of oxidative stress and signaling in this cell type.