Little is known about atrial natriuretic peptide metabolism or secretion in the human fetus. The purpose of this study was to determine if both the placenta and umbilical vessels are possible sites of atrial natriuretic peptide metabolism and to evaluate the effects that labor, route of delivery, prolonged pregnancy, preeclampsia, and fetal distress have on umbilical arterial atrial natriuretic peptide levels. We found that plasma atrial natriuretic peptide levels in the umbilical artery are significantly greater than those in the vein (p less than 0.001). Umbilical arterial and umbilical venous atrial natriuretic peptide levels were higher in plasma samples collected immediately at delivery when compared with those obtained 10 minutes later (p less than 0.001). Umbilical arterial atrial natriuretic peptide levels were elevated in pregnancies complicated by preeclampsia and fetal distress (p less than 0.01). Labor, route of delivery, and prolonged pregnancy had no effect on umbilical arterial atrial natriuretic peptide levels. We propose that both the placenta and umbilical vessels contain atrial natriuretic peptide receptors that are involved in the clearance or metabolism of atrial natriuretic peptide. The increased umbilical arterial atrial natriuretic peptide levels present in preeclampsia and fetal distress may reflect an attempt by the fetus to regulate blood flow.