Negative iron balance is experienced by premature infants undergoing rapid growth, iatrogenic phlebotomy loss or treatment with r-HuEPO unless treated with exogenous iron or RBC transfusion. Treatment with iron risks oxidant injury as a result of iron's role as a catalyst generating hydroxyl radicals(•OH) in the Haber-Weiss reaction. To test for lipid and protein •OH injury, plasma and urine of newborn lambs treated with iv iron were tested by HPLC for malondialdehyde (MDA) and ortho-tyrosine (o-TYRO). Beginning on 3-5 d of life, lambs were treated with 2 or 12 mg/kg i.v. saccharated iron (Ferrum iv Hausmann®, St. Gallen, Switz) 3x/wk for 11 d. Although plasma and urinary MDA and o-TYRO levels (mean ±SD) were not increased in samples taken 2-3 days post-iron treatment, 2- to 3-fold increases were found 1-3 hours after iv dosing at 12 mg/kg: Table When plasma MDA and o-TYRO levels were correlated with plasma iron, both demonstrated significant direct associations (r = 0.72, P< 0.02, and r =0.92, P < 0.001, respectively). We conclude that rapid iv injection of saccharated iron at a dose of 12 mg/kg results in transient lipid and protein •OH damage. Since this dose of iron is 7-fold higher than in utero iron accretion, it is possible that smaller doses of parenteral iron administered more slowly can avoid•OH injury yet provide adequate nutritional iron for growth and stimulated erythropoiesis.