OBJECTIVE: Our purpose was to study the localization, distribution of binding sites, and contractile effects of endothelin-1 in human uteroplacental smooth muscle. STUDY DESIGN: The tissue localization of endothelin-1, the distribution of iodine 125-labeled endothelin-I binding sites, and the mechanical effects of endothelin-1 were studied in isolated tissues from the human uterus and placenta by immunocytochemistry, autoradiography, and organ bath experiments. RESULTS: No specific endothelin-1 immunoreactivity could be detected in fetal placental tissues or in myometrium or intramyometrial arteries from term pregnant and nonpregnant women. In placental tissues a high density of iodine 125-labeled endothelin-1 binding sites was found in vessels of various sizes and in the chorionic villi, whereas the density in the jelly of Wharton was low. In myometrial tissue from pregnant and nonpregnant women a high density of iodine 125-labeled endothelin-1 binding sites was found, which in myometrium from pregnant women was mainly located to the myometrium and vascular smooth muscle. Endothelin-1 produced marked contractile responses in maternal and fetal uteroplacental vessels and in myometrial preparations. CONCLUSION: Endothelin-1 may be involved in the endogenous control of uteroplacental vascular and visceral smooth muscle.