AbstractThe gastrointestinal glutathione peroxidase (GI‐GPx) is the fourth member of the GPx family. In rodents, it is exclusively expressed in the gastrointestinal tract, in humans also in liver. It has, therefore, been discussed to function as a primary barrier against the absorption of ingested hydroperoxides. A vital function of GI‐GPx can be deduced from the unusual stability of its mRNA under selenium‐limiting conditions, the presence of low amounts of GI‐GPx protein in selenium deficiency where cGPx is absent, and the fast reappearance of the GI‐GPx protein upon refeeding of cultured cells with selenium compared to the slower reappearance of cGPx protein. Furthermore, the Secis efficiency of GI‐GPx is low when compared to cGPx and PHGPx. It is, however, almost independent of the selenium status of the cells tested. All these characteristics rank GI‐GPx high in the hierarchy of selenoproteins and point to a role of GI‐GPx which might be more crucial than that of cGPx, at least in the gastrointestinal system.