The effect of Maillard reaction products (MRPs) on induced DNA damage in human lymphocytes or HepG2 cells was investigated using comet assay. The undialyzed MRPs (xylose-lysine, glucose-lysine and fructose-lysine MRP) caused significant DNA damage in lymphocytes at a concentration of 0.05–0.1 mg/ml. The undialyzable xylose-lysine and glucose-lysine MRP caused significant DNA damage in lymphocytes at a concentration greater than 0.1 mg/ml. Both undialyzable and undialyzed MRPs also caused significant DNA damage in HepG2 cells. MRPs caused greater DNA damage in lymphocytes than in HepG2 cells. Moreover, undialyzed MRPs caused less DNA damage than did undialyzable MRPs. The undialyzable MRPs did not affect the activity of glutathione (GSH) peroxidase or lipid peroxidation in lymphocytes. However, undialyzable MRPs decreased the GSH contents and the activities of GSH reductase and catalase in lymphocytes. From the results for the formation of 8-hydroxy-2′-deoxyguanosine, free radicals and hydrogen peroxide, the DNA damage in human cells induced by MRPs was due to the radicals produced in this reaction system.