Oxytocin (OX) has been suggested as a signal for parturition. Although OX is produced by both mother and fetus, concentrations are higher in umbilical than maternal blood. In addition, umbilical artery OX concentrations (15-40 pg/ml) are higher than umbilical vein (4-12 pg/ml) and maternal (1-10 pg/ml) concentrations. The umbilical A-V difference suggests that placental uptake and transport may be one path from fetal (F) to maternal (M) circulation. However, this difference may also reflect placental oxytocinase activity, which is known to metabolize biologically active peptides such as OX. We have investigated placental transport of OX from F to M and M to F circulation using in vitro dually perfused isolated cotyledons from term human placenta. Term human placentae from uncomplicated pregnancies were obtained immediately after delivery. A single peripheral cotyledon and corresponding lobule was cannulated and perfused. After stabilization and demonstration of adequate M to F perfusion-perfusion overlap, we studied the transport of OX (3H) with 14C-inulin (14C-IN) as permeability reference in both M to F (n = 8) and F to M (n = 6) directions during 2 h of perfusion. In addition to the higher tissue uptake observed in M to F than F to M transport direction as measured by the drop in the concentration of both 3H-OX and 14C-IN in the circuits in which both compounds were added, the same trend was found for the transfer rates of both compounds. These transfer rates which reflect the permeability of placental tissue to OX and IN were 15.17 +/- 2.79 (mean +/- SD) and 6.28 +/- 0.93 microliters/min/g (M to F) and 11.79 +/- 1.77 and 4.91 +/- 0.81 microliters/min/g (F to M). Although the permeability of both compounds is higher in the M to F than in the F to M transport direction, comparing these permeability values with respect to their molecular weight (MW) showed a significant correlation when known permeability values of polar compounds between MW 60 and 68,000 daltons were included. This correlation indicates that OX crosses the placenta in both directions by simple diffusion. High-performance liquid chromatography analysis showed that there is little evidence of placental metabolism and degradation of OX over the period of these experiments. Oxytocin is the main therapeutic drug that is frequently used in obstetrics for the induction of labor and parturition. Under such circumstances and with respect to the placental permeability results, oxytocin could reach the fetal circulation.