Maintenance of appropriate intracellular glutathione (GSH) levels is crucial for cellular defense against oxidative damage. A suggested mechanism of methylmercury (MeHg) neurotoxicity implicates the involvement of oxygen radical formation and a decrease in cellular levels of GSH. Astrocytes play an important role in providing GSH precursors to neurons, and as will be discussed in this review, altered GSH homeostasis likely leads to impairment of astrocytic handling of glutamate, and neuronal energy metabolism. The review summarizes recent observations on transport systems for cysteine and cystine, precursors of GSH, in primary cultures of astrocytes and neurons, and their sensitivity to MeHg treatment. © 2001 Wiley-Liss, Inc.