Mongolism, or Down's syndrome (DS) is an inborn pathology due to trisomy 21. Apart from mental deficiency and anatomical abnormalities, premature aging is characteristic for this disease. This paper mainly reviews data on the generation of reactive oxygen species (ROS) and antioxidative defense mechanisms in DS, and on the sensitivity of DS cells to model sources of ROS. Changes in the antioxidative defense of DS cells are due mainly to the location of the gene for (Cu,Zn)-superoxide dismutase on chromosome 21. It is suggested that a disturbance of balance of ROS may be a key point in the pathogenesis of DS.