Endothelin (ET) was originally isolated from culture medium of porcine aortic endothelial cells as a potent vasoconstrictor peptide.Subsequently, ET was also reported to be produced by nonvascular tissues and to be involved in various biological phenomena in these tissues.Recently, a high concentration of ET-1-like immunoreactivity (ET-1-LI) was found in human amniotic fluid.Amnion tissue also contained a large amount of ET-1-LI, and cultured amnion cells secreted large amounts of ET-1-LI.The major component of ET-1-LI in these samples was ET-1.Moreover, the expression of prepro-ET-1 mRNA was detected in both amnion tissue and cultured amnion cells, indicating that ET-1 in the amniotic fluid originated from amnion cells.In cultured amnion cells, ET-1 secretion was stimulated by EGF, TGF-β, IL-1α, β and TNF-a.In addition, specific receptors for ET, ET-AR and ET-BR were detected in myometrium, decidua vera, chorion laeve, and placenta at term by both ligand binding and Northern blot analysis.These findings suggest that ET-1 secreted from amnion cells plays a physiological role in human pregnancy.In this paper, the regulation of production of ET-1 and expression of receptors for ET-1 by avascular human amnion tissue are reviewed.The possible importance of amniotic ET in human pregnancy is also discussed.