Gender and maturation affect glutathione status in human neonatal tissues. The objective was to verify if human tissues derived from baby girls had a greater ability then tissues derived from males to stimulate the glutathione-reductase, when faced with an oxidative challenge. In vitro, the effect of a calibrated oxidative challenge was studied in endothelial cells. In vivo, the effect of a clinically relevant oxidative challenge was studied in cells from tracheal aspirates derived from oxygen-dependent newborn infants. In endothelial cells, the oxidant tert-butylhydroperoxide had a stimulating effect on GSSG-R activity in cells derived from females. The peroxide produced a time, concentration and gender-dependent cytotoxicity, with female-derived cells exhibiting a better viability. In vivo, the intracellular total glutathione content was higher in female-derived cells and in cells from more mature babies; postnatal age and gestational age had a positive effect on the activity of GSSG-R. Oxygen (FiO2 > or = 0.3) was associated with a lower activity of GSSG-R in boys, early in life. Considering that glutathione is a central element in the antioxidant defense, these results suggest that specific tissues derived from the baby girl are potentially better protected against an oxidative stress than those derived from the boy.