The objective of this study is to determine the possibility that pre-eclampsia, a disease characterized by altered vascular tone, may result in altered levels of fetal BNP and cGMP, and to determine whether pre-eclampsia alters the maternal-fetal relationship of BNP and cGMP. Paired maternal and umbilical venous plasma levels of BNP and cGMP were determined in 13 pre-eclamptic and 9 normotensive primigravidas in the third trimester. Statistical analysis was performed using multivariate analysis of variance, linear regression, and canonical correlation. Overall, levels of cGMP were lower in pre-eclampsia (P < 0.03). Pre-eclampsia was also associated with an altered maternal-fetal relationship for BNP and cGMP (P < 0.008, P < 0.02, respectively). With pre-eclampsia, the maternal:fetal ratio was reduced for BNP and was increased for cGMP. Because of its role as a second messenger for many vasoactive hormones, we hypothesize that fetal cGMP levels may better reflect overall vascular tone than do individual hormones. Altered BNP and cGMP maternal-fetal homeostasis raises the possibility of maternal-fetal coordination of vascular control.