Unlike the findings in animal studies, in which a decline in progesterone levels is clearly associated with the onset of labor, investigation of progesterone levels among human parturients has resulted in controversy.This study was designed to address the issue and evaluate labor-onset related changes of estradiol-progesterone(E2-P) concentration in fetal scalp serum, umbilical vein serum and in the peripheral maternalserum. Seven women in spontaneous labor, were compared to 7 women in whom labor was induced. Our results reveal a significant decrease in the maternal serum P concentration when spontaneous labor is taking place (120.6 ± 24.5 mg/ml versus 177.3 + 61.4 mg/ml, p < 0.05). Significant change in the ratio of the fetal scalp to the maternal serum E2/P ratio in women at spontaneous labor versus induced labor is also shown. We could not demonstrate any changes in the E2 levels in relation to labor. We conclude that the onset of labor in human pregnancy is most probably preceded by local changes in the levels of P and ratio of P to E2. These changes may play an important regulatory role in onset of labor.