In the fetal-to-neonatal transition, important circulatory and respiratory changes ensue which lead to oxidative stress evidenced by changes in glutathione status. Administration of N-Acetyl-Cysteine (NAC), a glutathione precursor, to the mother might be a rational approach to protect the fetus against oxidative stress. We have found that NAC administration to pregnant rats partially prevents the change in hepatic GSSG that occurs in the fetal-neonatal transition: GSSG increased 11-fold (from 1 to 12 nmol/g) in controls and less than two-fold (from 5 to 9 nmol/g) in animals exposed to NAC in utero. The GSH/GSSG ratio in liver of NAC-treated newborns was 411 +/- 216 and in liver of controls it was 283 +/- 176. Thus, the oxidative stress that occurs in the fetal-to-neonatal transition is partially prevented by oral NAC administration.