Ascorbic acid (AA), a plasma antioxidant, is maintained at high levels in premature fetal blood and declines rapidly postpartum. The sudden reduction in blood AA levels secondary to premature delivery may increase the risk of oxidant injury, that is, bronchopulmonary dysplasia and intraventricular hemorrhage. There is concern that administration of AA to premature infants, in an effort to increase antioxidant capacity, may cause hemolysis. We felt that the benefits of early AA administration and prevention of the immediate postnatal drop in blood AA levels, might outweigh the risks of erthrocyte damage. Fifty one high-risk premature infants were randomized to receive either normal saline or 100 mg/kg of AA, daily for the first week of life. Double-blind comparisons were made of hemoglobin, hematocrit, erythrocyte morphology, bilirubin, number of blood transfusions and days of phototherapy, renal function tests, the incidence of infection, bronchopulmonary dysplasia, and intraventricular hemorrhage during the first month of life. The administration of AA prevented the immediate postnatal drop in AA and was not associated with evidence of increased hemolysis. No significant differences in renal function, rate of infection, bronchopulmonary dysplasia, or intraventricular hemorrhage were seen between the two groups. This study suggests that AA administration to the premature infant is safe and supports the designing and performance of larger clinical studies of the antioxidant properties of AA.