Glutathione peroxidase (GSH-Px), a selenocysteine-containing enzyme, is generally considered to be important in protecting animals from oxidative injury. However, guinea pigs have very low GSH-Px activity in major tissues such as liver and kidney, while the activity in the erythrocytes is as high as that of mice or rats. The present study attempted to clarify which step in the gene expression of GSH-Px is responsible for the tissue specific regulation of GSH-Px activity in guinea pigs. Northern blot analysis showed clear signals of GSH-Px mRNA in the reticulocytes and erythroblast-enriched bone marrow cells of guinea pigs, while it was barely detectable in the liver, kidney and heart. Using the nuclear run-on assay, we confirmed that the difference in GSH-Px mRNA levels among tissues of guinea pigs results primarily from the difference in the transcription rate of the GSH-Px gene. Thus, the guinea pig may be a good model for studying the factors regulating the tissue-specific gene expression of this selenoenzyme as well as its essential role.