Silymarin is a polyphenolic plant flavonoid (a mixture of flavonoid isomers such as silibinin, isosilibinin, silidianin and silichristin) derived from Silymarin marianum that has anti-inflammatory, hepatoprotective and anticarcinogenic effects. Our earlier studies have shown that silymarin plays a protective role against the oxidative damage induced by environmental contaminants like benzo(a)pyrene in erythrocyte haemolysates. During the detoxification of these environmental contaminants, the major reactive oxygen species generated is hydrogen peroxide (H(2)O(2)). Because H(2)O(2 )can easily penetrate into the cell and cause damage to biomolecules, the protective role of silymarin was further assessed against this cytotoxic agent in vitro in erythrocyte haemolysates. The protective effect was monitored by assessing the levels of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-s-transferase, glutathione peroxidase and malondialdehyde (LPO) in three groups: vehicle control, H(2)O(2)-exposed groups and drug co-incubation group (H(2)O(2) + silymarin). The protective effect of silymarin on the non-enzymic antioxidant glutathione and haemolysis, methaemoglobin content and protein carbonyl content were also assessed. It was observed that the activities of antioxidant enzymes and glutathione were reduced and the malondialdehyde levels were elevated after H(2)O(2 )exposure. There were also alterations in haemolysis, methaemoglobin content and protein carbonyl content, whereas after the administration of silymarin, the antioxidant enzyme activities reversed to near normal with reduced malondialdehyde content and normalized haemolysis, methaemoglobin content and protein carbonyl content. The results suggest that silymarin possesses substantial protective effect and free radical scavenging mechanism against exogenous H(2)O(2)-induced oxidative stress damages, hence, can be used as a protective drug against toxicity induced by environmental contaminants.