Compression trauma of the cat spinal cord induces a very rapid alteration in the lipid metabolism of cellular membranes, including lipid hydrolysis with release of fatty acids including arachidonate, production of biologically active eicosanoids, and loss of cholesterol. This disturbance of cellular membranes can directly damage cells and can lead to the secondary development of tissue ionic imbalance, ischemia, edema, and inflammation with neuronophagia. Pretreatment with either the synthetic glucocorticoid methylprednisolone sodium succinate (MPSS) or the antioxidants vitamin E and selenium (Se) completely prevented the loss of cholesterol and partially inhibited lipolysis and prostanoid production. Treatment with MPSS significantly reduced the postinjury tissue necrosis and paralysis. Preliminary evidence indicates that pretreatment with vitamin E and Se also protected against the effects of spinal cord injury (SCI). We speculate that the ability of these agents to preserve function after SCI may, in part, reside in their capacity to limit the trauma-induced changes in lipid metabolism.