Fetal oxytocin contribution to the mother during spontaneous labor was investigated using a specific and sensitive radioimmunoassay to measure oxytocin in blood, amniotic fluid, and urine. In 26 subjects with spontaneous labor and vaginal delivery (Group I) and 18 subjects with cesarean section after labor (Group II), umbilical arterial plasma (UA) oxytocin concentrations were significantly higher than umbilical venous plasma (UV) ocytocin concentrations. With elective cesarean section (Group III), UA oxytocin concentration was 29.8 ± 7.5 pg/ml and UV oxytocin concentration was 16.1 ± 5.9 pg/ml (n=14). In contrast, the mean UV oxytocin concentration was higher than the mean UA oxytocin concentration, when oxytocin was given to the mother (Group IV). The arterio-venous (A-V) difference in oxytocin concentration in Groups I and II was significantly higher than in Group III. Amniotic fluid oxytocin concentrations in Group I and II patients were higher than in Group III. Oxytocin was also present in fetal urine. The findings indicate that during spontaneous labor, oxytocin is produced by the fetus and flows toward the maternal circulation.