N-terminal peptide of pro-opiomelanocortin (N-POMC) was measured in the human amniotic fluid. At the gestational age of 16 to 20 weeks, the radioimmunoassay with three different antibodies demonstrated the respective values of 2.39 +/- 0.78, 4.69 +/- 2.27, and 5.92 +/- 2.66 ng/ml. These values are approximately 10 times higher than the measurements in the plasma of women at the corresponding gestational period. The amniotic fluid collected during the delivery had significantly lower concentrations of N-POMC than the amniotic fluid at 16 to 20 weeks' gestation. However, the plasma values of N-POMC had increased approximately three times when measured at delivery and compared with the plasma values at 16 to 20 weeks' gestation. Adrenocorticotropic hormone, measured simultaneously with N-POMC in some of the samples, showed changes similar to those in N-POMC. The N-POMC immunoreactivity from the amniotic fluid has the same retention time on reversed-phase high-performance liquid chromatographic separation as the peptide purified from the human pituitary gland, thus indicating the identity of both peptides.