Human umbilical cord contains two arteries and a vein surrounded by Wharton's jelly with amnion covering the exterior surface. The cord blood and amniotic fluid contain human CG (hCG). Whether hCG can directly regulate cord functions is unknown. We now report that human umbilical cords contain a major 4.4-kilobase and minor 2.6- and 1.8-kilobase hCG/LH receptor messenger RNA transcripts. The cords also contain a 50-kilodalton immunoreactive receptor protein which can bind hCG and LH, but not hFSH or hTSH. Rat testis used as a positive tissue control contained the same major and minor receptor transcripts and an 80-kilodalton receptor protein which can bind [125I]hCG. Rat liver used as a negative control contained neither receptor transcripts nor receptor protein. The smooth muscle and endothelial cells of umbilical arteries and vein, umbilical amnion, and cells in Wharton's jelly contain the receptor transcripts and receptor protein which can bind [125I]hCG. The receptor expression was higher in umbilical vessels closer to the baby and decreased toward placenta, becoming barely detectable once the vessels were inside the placental tissue. In vitro treatment of umbilical cords with highly purified hCG resulted in an increase of immunoreactive cyclooxygenase-1, cyclooxygenase-2, prostacyclin synthase, and 6-keto-prostaglandin F1 alpha, little change in thromboxane A2 synthase and a decrease of prostaglandin E2 and thromboxane B2 as compared to the controls, indicating that the cord receptors are functional. In summary, these novel findings suggest that hCG present in cord blood and amniotic fluid may directly regulate the vascular tone and quite possibly other functions of human umbilical cord.