Important changes take place in the maternal uterine vasculature during the first few weeks of pregnancy resulting in increased blood flow to the developing fetus. Vascular endothelial and smooth muscle cells are lost from the spiral arteries and are replaced by fetal trophoblast cells. Failure of the vessels to remodel sufficiently in the first trimester is a common feature of pregnancy pathologies such as early pregnancy loss, intrauterine growth restriction and pre-eclampsia. There is evidence to suggest that some vascular changes occur prior to trophoblast invasion, however, in the absence of trophoblasts remodelling of the spiral arteries is greatly reduced. Until recently our knowledge of these events has been obtained from immunohistochemical studies which, although extremely useful, give little insight into the mechanisms involved. We have development in vitro models including co-culture, time-lapse microscopy and spiral artery perfusion systems to investigate these events at a cellular and molecular level we are beginning to get a clearer picture of the regulation of spiral artery remodelling at the materal-fetal interface. Trophoblasts synthesise and release a number of cytokines and growth factors including members of the tumour necrosis factor family. Our studies suggest that these factors may be important in regulating the remodelling process by inducing both endothelial and vascular smooth muscle cell apoptosis. More recently we have examined the role of maternal immune cells and in particular decidual natural killer cells in this complex process and have identified factors that they release that not only increase the motility of trophoblasts but also assist in remodelling by inducing vascular cell apoptosis. Studies into the aetiology of pre-eclampsia are hampered by the lack of an appropriate animal model and the inability to identify in the first trimester those individuals destined to develop pre-eclampsia. To address this we have used uterine artery Doppler ultrasound scanning to screen first trimester pregnancies in women attending clinics for surgical termination of pregnancy. Using this approach we have established significant differences in remodelling processes in pregnancies that are most and least likely to have developed pre-eclampsia.