Endothelins (ETs), recently discovered and highly vasoactive substances, have been implicated in the pathogenesis of various perinatal problems, such as preeclampsia, intrauterine growth retardation, intraventricular hemorrhage, pulmonary hypertension and necrotizing enterocolitis. Although fetal ET levels have been measured at birth, reference ET values for healthy newborns in the first days of life have not been established. The purpose of this study was to determine in normal healthy neonates ET 1-21 plasma values on day 1 and 4 postpartum and to investigate possible changes after adaptation of the newborn to extrauterine life. The study comprised 20 healthy full-term neonates, born after vaginal delivery (n = 10), or cesarean section (CS; n = 10) because of a previous CS. Venous blood was drawn on day 1 and 4 from all neonates and ET 1-21 levels were determined in the plasma by radioimmunoassay (Amersham kit RPA 5559). ET 1-21 values were on day 1 11.83 +/- 2.39 pmol/l (n = 20) and on day 4 9.45 +/- 1.88 pmol/l (n = 20). The statistical analysis showed a significant reduction of plasma ET levels on day 4 (p = 0.004), but no influence of the mode of delivery on plasma ET levels. In conclusion irrespective of the mode of delivery the high ET 1-21 plasma levels on day 1 postpartum are significantly reduced on day 4 of life.