Kashin-Beck disease (KBD) is a chronic osteoarthritic disease, endemic in parts of China. Its etiology is unknown. Selenium deficiency, high concentration of organic matter (mainly fulvic acid) in drinking water, and severe contamination of grain by fungi have been proposed environmental causes. Free radicals, possible mediators between the environmental factors and origin of KBD, have been studied in this work. Drinking water from KBD-affected areas contains a higher level of semiquinone radicals than that from disease-free areas. In animal experiments, fulvic acid (FA) accumulated in the skeletal system as semiquinone radicals. Contamination of grain by Fusarium oxysporum or Alternaria alternata significantly increased the content of semiquinone radicals. Furthermore, corn grown in endemic areas had a higher content of radicals than that from disease-free areas. The g factor values for these radicals from contaminated corn were about 2.0040, in the range of semiquinone radical. In monolayer culture of human embryonic chondrocytes, FA and aqueous extracts of grain contaminated by Fusarium injured the chondrocytes and enhanced lipid peroxidation. Selenite and superoxide dismutase (SOD) protected the cells from injury by these toxins and reduced lipid peroxide. Lower glutathione peroxidase activities and higher levels of lipid peroxidation were also found in the children living in KBD-affected regions. Thus, FA and the mycotoxin, which are seen as exogenous free-radical carriers, are important environmental factors in the pathogenesis of Kashin-Beck disease; and selenium, vitamin C, and vitamin E, which inhibit free-radical formation, are considered to be protective.