To determine whether S100beta, an acidic calcium-binding protein previously demonstrated as a reliable indicator of a brain lesion, could be helpful in the detection of brain distress in intrauterine growth-retarded (IUGR) fetuses, we studied, by a case-control study, the correlation between S100B protein and the degree of fetoplacental blood flow impairment. Maternal and umbilical blood samples and placental tissue specimens were collected at delivery from IUGR pregnancies with normal (n = 10) or abnormal (n = 10) umbilical artery Doppler findings and from 40 uncomplicated pregnancies. S100beta protein levels were measured by means of a specific RIA, and flow velocimetry waveforms were recorded from uterine, umbilical, and fetal middle cerebral arteries. Overall mean S100beta proteins in umbilical plasma levels were higher (p < 0.05) in IUGR patients (121.8 +/- 70.4 fmol/mL) than in control patients (54.7 +/- 21.9 fmol/mL). IUGR fetuses with redistribution of blood flow showed the higher concentration of the protein (163.7 +/- 55.2 fmol/mL). Fetal S100beta concentrations correlated with middle cerebral artery pulsatility index (r = -0.536, p < 0.03) and with umbilical artery pulsatility index to middle cerebral artery pulsatility index ratio (r = 0.469, p < 0.03). No difference in the localization or intensity of S100beta staining in the placental tissues or cord between uncomplicated and IUGR pregnancies was found. This study provides evidence that circulating S100beta protein is increased in IUGR fetuses and correlates with cerebral hemodynamics, suggesting that it may represent an index of cerebral cell damage in the perinatal period.