Chronic obstructive pulmonary disease (COPD) is a major problem in industrialized countries. Much evidence suggest that oxidative stress has been associated with chronic diseases, including COPD. There are a number of good experimental and clinical studies clearly showing a strong relationship between oxidative stress and DNA-damage in several diseases. The present study was aimed at establishing whether genome damage is also exists in COPD. Prooxidant therapy mediates its action through the development of oxidative stress that can lead to oxidative modification of DNA. The role of ozone in the genome damage has received little attention. The genotoxicity of ozone is of interest because ozone therapy is used for the treatment of various chronic conditions, including COPD and may impose a possible risk of genotoxic effects for patients. The purpose of this study was to investigate genotoxic effect of different dosing schedules of prooxidant therapy in vitro on the blood of patients with COPD. Peripheral blood was obtained from 20 COPD patients and 15 age- and sex-matched controls. Our present results have shown that ozone induces DNA-damage in human blood cells in vitro. The severity of oxidative DNA-damage in COPD patients directly depends on the concentration of ozone. Clinical results have shown that DNA-damage is an important part of the pathogenesis of the chronic inflammatory process in the bronchopulmonary system.