beta-Endorphin immunoactivity was measured in the plasma of 50 pregnant women, 25 nonpregnant women, 19 women during labor, and 25 women at the time of vaginal delivery. Simultaneous maternal and umbilical cord plasma samples were obtained in 23 cases. Mean beta-endorphin immunoactivity in the pregnant women was 15.6 +/- 1.6 pg/ml. No significant differences in mean beta-endorphin concentration were found in the first, second, or third trimesters until after the onset of labor, and at no time during this interval did levels differ from the mean of 12 +/- 1.9 pg/ml found in nonpregnant controls. In early labor, beta-endorphin was not elevated (14.8 +/- 2.3 pg/ml), but rose in the later stages of labor (cervical dilatation, > 4 cm) to 70.3 +/- 8.2 pg/ml and peaked during delivery at 113 +/- 13.3 pg/ml. Chromatography of plasma from women at delivery, pregnant women not in labor, and nonpregnant controls to separate beta-endorphin from cross-reacting beta-lipotropin showed mean beta-endorphin to beta-lipotropin molar ratios of 0.22-0.27 in the three groups, with no significant differences among the groups. In 23 subjects in whom simultaneous maternal and umbilical cord plasma samples were obtained, there was no correlation between the beta-endorphin immunoactivity in the paired samples, supporting the concept that fetal beta-endorphin is not of maternal origin. In 13 fetal umbilical cord samples, ACTH was measured in addition to beta-endorphin immunoactivity. A close correlation (r = 0.836) was observed between the concentrations of the two peptides, suggesting that in the fetus, as in the adult, beta-endorphin and ACTH are processed in parallel from a common precursor.