Selenoprotein P (SeP) is a plasma protein which contains 10 selenocysteine residues per polypeptide. It accounts for more than 50% of the selenium content in rat and human plasma but its function is still not completely understood. However, a function as an extracellular antioxidant seems most probable. A protective function of SeP in human plasma against the potent endotoxin peroxynitrite and phospholipid hydroperoxide reducing activity was demonstrated in vitro. An association of SeP with the vascular endothelium, a prime target of peroxynitrite toxicity, was shown in vivo. SeP of bovine serum acts as a survival-promoting factor in neuronal cell culture. Analysis of the human SeP promoter indicates a transcriptional regulation of SeP by inflammatory mediators.