Nerve growth factor is a neurotrophic factor which promotes cell survival and differentiation in the central and peripheral nervous system. The rat pheochromocytoma (PC12) cell has been frequently used to study the actions of nerve growth factor (NGF). Our previous studies demonstrate that pretreatment with NGF for 24 h protects PC12 cells from oxidative stress by increasing glutathione (GSH) concentrations and the activity of gamma-glutamylcysteine synthetase, which is a rate-limiting enzyme in GSH synthesis. The synthesis of intracellular GSH is dependent on the availability of the precursor amino acid, L-cysteine. Cells take up L-cystine from the extracellular fluid and convert it to L-cysteine intracellularly. L-Cysteine is then released from cells to maintain extracellular L-cysteine. Here we report that NGF increased the uptake of L-cysteine or L-cystine. The increased concentrations of L-cysteine or L-cystine by NGF was responsible for the enhanced intracellular GSH concentrations. The increased GSH and L-cysteine concentrations by NGF also served as intracellular antioxidants. The protection of PC12 cells by NGF from oxidative stress was due to the stimulated increased levels of intracellular glutathione and L-cysteine or L-cystine.