Adrenomedullin (AM) is a peptide that elicits a long-lasting vasorelaxant activity, while atrial natriuretic peptide (ANP) has also been shown to be a potent vasodilatory agent. To clarify the possible role of AM and ANP in the physiology of pregnancy and pathophysiology of pre-eclampsia, we measured plasma concentrations of these peptides in non-pregnant women, normal pregnant women and women with pre-eclampsia. A gradual increase in plasma AM was observed as pregnancy progressed. The plasma AM concentrations during the second trimester (12.7 ± 1.4 fmol/ml) were significantly elevated, in comparison with the non-pregnant follicular phase (6.4 ± 0.61 fmol/ml), luteal phase (6.0 ± 0.49 fmol/ml), and the first trimester (6.5 ± 0.8 fmol/ml). The plasma AM concentrations of the third trimester (21.5 ± 1.4 fmol/ml) were significantly elevated when compared with those of the second trimester (P < 0.05). Northern blot analysis confirmed the expression of the AM mRNA transcript (1.6 kb) in third trimester placentas. In comparison with those observed at term (25.3 ± 4.5 fmol/ml), the plasma concentrations were significantly reduced post-partum (6.4 ± 0.6 fmol/ml). In the third trimester, plasma AM concentrations did not differ significantly between women with pre-eclampsia (17.2 ± 2.3 fmol/ml) and normal pregnant women. In contrast, the plasma ANP concentrations in pre-eclampsia (39.5 ± 7.1 pg/ml) were significantly elevated when compared with those of the normal third trimester (14.4 ± 1.4 pg/ml) (P < 0.05). ANP concentrations were reasonably constant throughout the pregnancy.