Objective: The aim of this study was to determine the physiologic role for endogenous endothelin in the regulation of vascular tone during normal pregnancy and preeclampsia. The vascular sensitivity to endothelin-1 during pregnancy was studied also. Study design: Forearm blood flow was measured by venous occlusion plethysmography during intraarterial infusion of phosphoramidon, an endothelin-converting enzyme inhibitor, for 60 minutes, which was followed by co-infusion with endothelin-1 for 30 minutes. Three groups were studied: healthy nonpregnant women, normal pregnant women, and women with preeclampsia. Results: There was a significant increase in forearm blood flow in the nonpregnant group after phosphoramidon infusion alone (73% ± 37% ; P < .05). Phosphoramidon did not change forearm blood flow in pregnant subjects. Co-infusion with endothelin-1 significantly decreased forearm blood flow in both the nonpregnant and normal pregnant women (53% ± 7% and 40% ± 11% , respectively; P <.01). No response to endothelin-1 was found among women with preeclampsia. Conclusion: The vascular sensitivity to endothelin-1 is not altered during normal pregnancy in contrast to preeclamptic pregnancy, where no effect of endothelin-1 was seen. Reduced endothelin dependence during pregnancy might be one mechanism behind the fall in peripheral vascular resistance. Objective: The aim of this study was to determine the physiologic role for endogenous endothelin in the regulation of vascular tone during normal pregnancy and preeclampsia. The vascular sensitivity to endothelin-1 during pregnancy was studied also. Study design: Forearm blood flow was measured by venous occlusion plethysmography during intraarterial infusion of phosphoramidon, an endothelin-converting enzyme inhibitor for 60 minutes, which was followed by co-infusion with endothelin-1 for 30 minutes. Three groups were studied: healthy nonpregnant women, normal pregnant women, and women with preeclampsia. Results: There was a significant increase in forearm blood flow in the nonpregnant group after phosphoramidon infusion alone (73% ± 37%; P <.05). Phosphoramidon did not change forearm blood flow in pregnant subjects. Co-infusion with endothelin-1 significantly decreased forearm blood flow in both the nonpregnant and normal pregnant women (53% ± 7% and 40% ± 11%, respectively; P <.01). No response to endothelin-1 was found among women with preeclampsia. Conclusion: The vascular sensitivity to endothelin-1 is not altered during normal pregnancy in contrast to preeclampsia pregnancy, where no effect of endothelin-1 was seen. Reduced endothelin dependence during pregnancy might be one mechanism behind the fall in peripheral vascular resistance.