To examine the role of endothelin (ET) in the maternal and fetal circulation, the levels of endothelin-1-like immunoreactivity (ET-1-LI) in the plasma of maternal vein (MV), umbilical vein (UV), and umbilical artery (UA) were determined by a sensitive radioimmunoassay (RIA). Levels of ET-1-LI in MV did not show any significant change (9.9 +/- 1.5 pg/ml, n = 26) throughout normal pregnancy and were similar to those of normal nonpregnant women (10.7 +/- 2.5 pg/ml, n = 5). Levels of ET-1-LI in UV and UA obtained at normal deliveries at term were about three times higher than those in MV. In the patients with mild and severe pre-eclampsia, the levels of plasma ET-1-LI were significantly higher than those of normal pregnancy (14.3 +/- 2.2 pg/ml, n = 5 and 27.2 +/- 8.6 pg/ml, n = 5, respectively). However, in pregnant women with chronic hypertension, the levels of ET-1-LI did not increase when the hypertension did not worsen during pregnancy (11.4 +/- 1.6 pg/ml, n = 7). Moreover, in two pregnant women with abnormally stimulated coagulation, such as acute or subacute DIC, the levels of ET-1-LI were extremely high and returned gradually to those of normal nonpregnant women after the coagulation was normalized by treatment. These results suggest the possibility that ET-1 plays an important role in the pathophysiology of preeclampsia.