To investigate the transfer of fentanyl across the early human placenta, we have collected samples of maternal blood and fetal fluids and/or blood, simultaneously, between 5 and 22 min following an intravenous bolus of fentanyl (1.5 microg/kg) to the mother. The pregnancies were between 6 and 16 weeks of gestation and scheduled for elective termination of pregnancy under general anaesthesia. Total fentanyl concentration was determined by radioimmunoassay in 11 pairs of first trimester maternal serum and fetal coelomic fluid samples, 14 pairs of maternal serum and amniotic fluid samples, seven series of first trimester maternal serum and coelomic and amniotic fluid samples, and 10 series of early second trimester maternal and fetal sera and amniotic fluid samples. Fentanyl was not detected in coelomic fluid samples at any gestational age and in amniotic fluid samples collected after 12 weeks of gestation. Measurable concentrations of fentanyl were found in maternal serum collected within 15 min after the initial bolus and in fetal serum collected between 10 and 12 min later. These findings indicate that fentanyl is transferred across the early placenta into the amniotic cavity and fetal blood circulation but not into the exocoelomic cavity. The distribution of this molecule inside the early gestational sac is probably influenced by the increased binding by maternal and fetal sera, its short half-life of distribution and the specific biology of the fetal fluid formation and composition.