In normotensive nonpregnant women (n = 23), the plasma concentrations of immunoreactive endothelin-1 (ir-ET-1) were not different from nonpregnant women with essential hypertension (n = 15): 3.6 (2.0-5.4) ng/L (mean, range) versus 3.8 (2.4-5.8) ng/L. In normotensive pregnant women (n = 25), the plasma level of ir-ET-1 was 2.1 (1.3-3.4) ng/L (p < 0.01) lower than in normotensive nonpregnant women. Pre-eclamptic patients (n = 25) had elevated ir-ET-1 plasma levels of 5.0 (2.1-12.4) ng/L (p < 0.001 for normotensive pregnant women, p < 0.01 for nonpregnant women). The low level of ir-ET-1 in normotensive pregnant women may be explained by the increase in the distribution volume of ir-ET-1 during the course of pregnancy. Damage of vascular endothelium is a consistent morphological abnormality in pre-eclampsia. Elevated ir-ET-1 in plasma might be a biochemical marker of this abnormality and may contribute to the pathogenesis of pre-eclampsia.