Hemoglobin solutions were assessed in terms of their ability to promote lipid peroxidation, which was quantitated by measuring the formation of thiobarbituric acid reactive substances under specified conditions in murine brain homogenates. Solutions designed for use in acute treatment of hypovolemic shock and trauma should incorporate ingredients specifically aimed at decreasing oxygen and lipid radical mediated injury occurring secondary to ischemia and reperfusion. A number of strategies aimed at decreasing the oxidant effect of hemoglobin solutions and other blood and plasma substitues have been evaluated. These include use of the naturally occurring antioxidants in human plasma, specifically transferrin and ceruloplasmin. Similarly, certain iron chelators, such as deferoxamine, effectively prevent molecular and cellular damage caused by iron catalyzed formation of oxygen-derived radicals.