BACKGROUND The Fas-Fas ligand (FasL) pathway of apoptosis contributes to immune tolerance at the fetomaternal interface and has been ascribed a role in implantation and placental development. Intrauterine growth restriction (IUGR) may be associated with impaired maternal-fetal tolerance, resulting in increased trophoblast apoptosis and uteroplacental vascular insufficiency. OBJECTIVE To investigate soluble Fas (sFas) and FasL (sFasL) concentrations in maternal, fetal and neonatal serum of IUGR and appropriate-for-gestational-age (AGA) pregnancies. METHODS Circulating sFas and sFasL concentrations were determined in 40 mothers and their 20 IUGR (due to several etiologies) and 20 AGA singleton full-term fetuses and neonates on postnatal day 1 (N1) and 4 (N4). RESULTS No significant differences in sFas and sFasL concentrations were observed between groups. In both groups, maternal sFas concentrations were increased compared to fetal, N1 and N4 ones (p< or =0.005 in AGA and p < 0.001 in IUGR, in all cases). On the other hand, maternal sFasL concentrations were lower compared to fetal, N1 and N4 ones (p < 0.001 in all cases). Fetal sFasL concentrations were increased compared to maternal, but lower compared to N4 sFasL ones (p < 0.001 in AGA and p < or = 0.020 in IUGR, in all cases). N4 sFasL concentrations were elevated compared to N1 ones (p < 0.001). CONCLUSIONS Circulating maternal, as well as fetal sFas and sFasL concentrations do not differ between AGA controls and IUGR cases, irrespectively of the etiology of the latter. Furthermore, the results of this study imply an acceleration of Fas-FasL-mediated apoptosis during delivery and a respective decrease postpartum in both normal and IUGR pregnancies.