The effect of different doses of methylglyoxal (50-400 mg/kg body wt.) were examined using enzymes involved in the antioxidant function, glutathione (GSH) content and lipid peroxidation in the liver and spleen of Swiss albino mice (7-8 week old) after 6, 12 and 24 h. Significant changes were observed predominantly in the liver. The specific activities of superoxide dismutase (SOD), glutathione-S-transferase (GST), catalase, glyoxalase I (gly I) and glyoxalase II (gly II) were found to decrease in the liver. The mode and magnitude of change in the specific activities was seen to depend on the dose of methylglyoxal and the time after its administration. Methylglyoxal also decreased the GSH content and enhanced the lipid peroxidation in the liver. These findings are suggestive of the adverse effect of methylglyoxal on the antioxidant defence system. It is likely that methylglyoxal undergoes a redox cycle and generates the free radicals which in turn lower the antioxidant status in animals. The increased levels of lipid peroxidation provide support for the involvement of free radical processes in the detrimental effects of methylglyoxal. The response of DT-diaphorase (DTD) seems to be adaptive.