In a randomized trial to determine whether oral vitamin E reduced stages III and IV bronchopulmonary dysplasia (BPD) by 50%, 268 infants were randomly allocated, after stratification by birth weight and severity of disease, to receive vitamin E 25 units or an indistinguishable placebo. The experimental (E) group and the control (C) group were similar in weight, gestational ages, Apgar scores, severity of illness, and initial oxygen and ventilator exposure. Serum vitamin E levels were significantly different within 48 h of administration and remained well above normal adult levels from the first week of life in the experimental group. There was no difference in the rates of early death, BPD at 28 days, or mortality from BPD. Severity was similar and no difference was seen in the incidence of necrotizing enterocolitis or sepsis. There was no evidence that vitamin E supplementation offered protection against chronic lung disease in infants less than 1,500 g birth weight.