Extracellular glutathione peroxidase (EGPx) is a member of a selenium-dependent antioxidant enzyme family. To better understand its potential functions in vivo, we examined the postimplantation expression of EGPx mRNA from E7.5 to E16.5 of mouse development. During this period, the message for EGPx shifted major sites of accumulation, but maintained high concentration at borders between the developing embryo and its environment. Thus, at E7.5 (neural plate stage) the highest EGPx expression was found in the maternally-derived deciduum, with minor accumulation in the visceral yolk sac endoderm. At E9.5, the major sites of expression were the yolk sac endoderm and developing heart musculuture. By E16.5, EGPx mRNA expression persisted in the yolk sac endoderm, but also accumulated significantly in a ventral to dorsal gradient in the developing skin. Expression in the heart and lungs was primarily restricted to atrially-derived myocytes. At E16.5, we also detected significant EGPx mRNA accumulation in the intestinal epithelium and minor accumulation in developing kidney, the principle site of EGPx synthesis in the adult. Since EGPx is expressed in the yolk sac endoderm, we explored its in vitro expression in F9 teratocarcinoma cells. EGPx mRNA is induced along with α-fetoprotein when F9 cells are differentiated toward visceral, but not parietal endoderm. Further studies of EGPx function and gene regulation can now be performed in this in vitro system.