Following the observation that the level of glutathione in leukocytes from human newborn infants was lower in preterm and in male infants, a study was designed to document the level of activities of glutathione synthesis and gamma-glutamyltranspeptidase during the development of preterm and term newborn infants. Measurements were performed in leukocytes from tracheal aspirates of oxygen dependent infants, and in leukocytes from cord blood. Contrary to the common belief concerning the development of antioxidant activity, the biosynthesis of glutathione was active in leukocytes from preterm infants; and by two days of life the activity of gamma-glutamyltranspeptidase reached 3 times the level of that seen in cord blood. Our results suggest that the maturity of these enzymes was not the limiting step in maintaining cellular glutathione levels. This represents new information concerning the maturation of a central antioxidant in tissue derived from preterm and term human newborn infants at risk of oxidant stress. This implies that sources of cysteine crossing freely the cellular membrane could be used by tissues of term and preterm infants to produce glutathione.