AbstractThe tripeptide glutathione (GSH), which plays a crucial role in protecting cells against oxidative stress, is synthesized in a two‐step process. The rate‐limiting step is the binding of glutamate and cysteine, which is catalyzed by the enzyme glutamate‐cysteine ligase (GCL). This enzyme is composed of two subunits: a large catalytic subunit (GCLc) and a smaller modifying subunit (GCLm), originating from different genes. Control of cellular GSH levels is essential for normal development. In the current study, we investigated the tissue distribution of Gclc and Gclm transcripts, as well as GCLc protein, in the developing mouse embryo. We found that both mRNAs were highly expressed in the liver and CNS at gestational day 10 (gd 10) and gd 12, with Gclm being more abundant than Gclc in the liver relative to other tissues. Also, the expression of the two subunit mRNAs was not always parallel in the embryo, in that some tissues expressed one of the subunits preferentially, suggesting that the two genes are differentially expressed during mouse development. The GCLc protein was also widely expressed throughout the embryo, and, in general, it co‐localized with the Gclc mRNA. Mol. Reprod. Dev. 62: 83‐91, 2002. © 2002 Wiley‐Liss, Inc.