Serum vitamin E levels are reduced in newborn infants. It has been reported that this deficiency is responsible, in part, for the development of anemia in premature infants during the first 6 weeks of life. The efficacy of vitamin E supplementation for the prevention of anemia in premature infants has been studied in a randomized, controlled, and blinded trial. Premature infants whose birth weights were less than 1,500 g were given, by gavage, 25 IU of dl-alpha-tocopherol or a similar volume of the drug vehicle. Treatment was continued for the first 6 weeks of life. A total of 178 infants were studied. Vitamin E levels were significantly higher in a supplemented group by day 3 and for the remainder of the 6-week period. At 6 weeks of age, there was no significant difference between the supplemented and unsupplemented groups in hemoglobin concentration, reticulocyte and platelet counts, or erythrocyte morphology. It is concluded that there is no evidence to support a policy of administering vitamin E to premature infants to prevent the anemia of prematurity.