Chronic lymphocytic leukemia (CLL) is a neoplastic disease susceptible to antioxidant enzyme alterations and oxidative stress. We have examined the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and the oxidized/reduced glutathione (GSSG/GSH) ratio together with the levels of malondialdehyde (MDA) and 8-oxo-2'-deoxyguanosine (8-oxo-dG) in lymphocytes of CLL patients and compared them with those of normal subjects of the same age. SOD and CAT activity decreased in CLL lymphocytes while GPx activity increased. GSH content of CLL lymphocytes also increased, and GSSG concentration remained constant. Thus, a reduced GSSG/GSH ratio was obtained. The oxidation product MDA, and the damaged DNA base 8-oxo-dG were also increased in CLL. The observed changes in enzyme activities, GSSG/GSH ratio, and MDA were significantly enhanced as the duration of the disease increased in years. The results support a predominant oxidative stress status in CLL lymphocytes and emphasize the role of the examined parameters as markers of the disease evolution.