Trauma-induced lipid peroxidation (LP) is one of the most important factors that produces tissue damage in head trauma. In the present study, the protective effects of free radical suppression with methylprednisolone (MP), tirilazad mesylate (TM) and vitamin E on the development of cerebral LP and oedema resulting from head trauma have been investigated. Rats were divided randomly into four groups. Bolus injections of physiological saline, MP (initial 30 mg/kg for 1 h, continuing administration of 5.4 mg/kg per hour until 24 h), TM (10 mg/kg), or vitamin E (30 mg/kg) were given 1 h after the head trauma. The animals were killed 24 h after the weight-drop injury for removal of the brain, and the malondialdehyde (MDA) level and water content of the brain were determined. Rats treated with TM had MDA levels which decreased significantly in comparison with the control group (P<0.03), and none of the drugs had an effect on LP and water content of the brain (P>0.05) that was statistically different. These findings demonstrated the beneficial effect of TM in this model of experimental brain injury.