The purpose of this study was to investigate whether the fetus mounts a hormonal stress response to a potentially painful procedure, intrauterine needling. Cortisol and beta-endorphin concentrations in fetal plasma obtained during uncomplicated fetal blood sampling or intrauterine transfusions by needling the fetal intra-abdominal portion of the umbilical vein (intrahepatic vein) were compared to hormone concentrations in fetal plasma obtained by the conventional technique of needling the placental cord insertion, which is not innervated. Cortisol and beta-endorphin concentrations did not increase within 10 minutes of fetal abdominal needling (n = 15). However, more prolonged needling during transfusion at the intrahepatic vein was associated with an increase in fetal plasma cortisol (median increase 48 nmol/L; 95% Cl, 23-86) and beta-endorphin (207 pg/mL; 113-307) concentrations compared to transfusion at the placental cord insertion (p < 0.005 for both hormones). The magnitude of rise in hormone increased linearly with the duration of needling (cortisol, r = 0.80; beta-endorphin, r = 0.88, p < 0.05 for both). These data suggest that the fetus mounts a hormonal stress response to invasive procedures. They raise the possibility that the human fetus feels pain in utero, and may benefit from anaesthesia or analgesia for invasive procedures.