This study was designed to determine the presence of and possible changes in plasma and amniotic fluid immunoreactive neuropeptide-Y (irNPY) levels in pregnant women during gestation and at parturition. We studied 127 healthy pregnant and 12 nonpregnant women. The peptide was extracted from plasma or amniotic fluid with a propanolformic acid mixture and measured by RIA. The mean plasma irNPY concentration in 15 pregnant women during the first trimester of gestation was 129 +/- 12 (+/- SE) pmol/L, compared to 40 +/- 8 pmol/L in nonpregnant women (p less than 0.01). The mean values were 144 +/- 13 and 156 +/- 24 pmol/L, respectively, in 15 pregnant women during the second trimester and 33 women during the third trimester. These values did not differ from that during the first trimester. Amniotic fluid irNPY levels were similar to those in plasma and did not vary among the 3 groups of women studied during the various trimesters of gestation. During labor, plasma irNPY levels progressively increased, reaching the highest levels at the most advanced stages of cervical dilatation (greater than 8 cm, 351 +/- 38 pmol/L) and at the time of vaginal delivery (416 +/- 73 pmol/L). Plasma irNPY levels then decreased significantly 2 h after vaginal delivery. The amniotic fluid irNPY levels in women during the early or late stages of labor were similar. Moreover, plasma and amniotic fluid irNPY levels at the time of elective cesarean section also were similar. These results indicate that pregnant women have high plasma and amniotic fluid irNPY levels and that the stress of labor results in a further increase in plasma levels, suggesting a possible role of NPY in human pregnancy and parturition.