The objective of this study was to evaluate the effect of fetal blood sampling on ductus venosus hemodynamics. A secondary objective was to establish the relationship between the amplitude of these changes, if any, and different variables related either to the procedure of sampling or to fetal characteristics. The ratio was assessed between the systolic and atrial velocities from the ductus venosus that were measured immediately before and immediately after fetal blood sampling in 32 appropriately grown fetuses and in 12 growth-retarded fetuses. The latter group was characterized by abnormal Doppler indices in the umbilical artery and the middle cerebral artery, suggestive of uteroplacental insufficiency as the causative factor of the impaired growth. The systolic/atrial ratio fell significantly after fetal blood sampling, but this decrease was less evident in growth-retarded fetuses. Neither the site of needling (placental cord insertion or intrahepatic vein) nor transplacental puncture during the procedure affected this decline. Similarly, fetal smallness, the volume of fetal blood aspirated and baseline values in Doppler indices from the ductus venosus and middle cerebral artery were unrelated to the observed changes. Stepwise regression analysis indicated that the variables that most significantly and independently affect the decline of the Doppler index were gestational age at the time of the procedure and pO2 values in the umbilical vein. In conclusion, modifications in ductus hemodynamics are induced by fetal blood sampling. These changes are less evident in hypoxemic growth-retarded fetuses and this reduced hemodynamic response may explain the higher rate of complications occurring in such fetuses after blood sampling.