Controversy exists as to whether the parenterally (PN) fed human neonate is capable of synthesizing adequate cysteine from methionine if the total dietary requirement for sulfur amino acid (SAA) is provided as methionine only. The goal of this study was to gather data on whether glutathione (GSH) synthesis is maximized at a methionine intake previously shown to be adequate for protein synthesis in the PN-fed human neonate. We measured GSH concentration, fractional, and absolute synthesis rate in five PN-fed human neonates. Each neonate underwent two isotope infusion studies of 7 h duration after a 2-d adaptation to the total SAA requirement (methionine only) and again after a further 2-d adaptation to the same methionine intake supplemented with cysteine at 10 mg x kg(-1) x d(-1). Cysteine supplementation did not significantly affect GSH synthesis. These data suggest that term infants are capable of synthesizing cysteine from methionine, not only for protein but also for GSH synthesis.