In view of the pathological placental features of pre-eclampsia and intrauterine growth restriction (IUGR), and the angiogenic effects of vascular endothelial growth factor (VEGF), the aim of this study was to determine the expression of VEGF in placentae from normal pregnancies and to compare the results with placentae from pregnancies complicated by pre-eclampsia and intrauterine growth restriction (IUGR). ELISA was used to measure circulating VEGF immunoreactivity in umbilical vein serum samples and immunohistochemistry was used to determine tissue expression of the protein. Since VEGF is known to be upregulated by hypoxia, the expression pattern of VEGF would provide further clues to the oxygen status in the placentae at the time of sampling, presently a subject under great debate. The geometric mean concentration of VEGF immunoreactivity in umbilical vein serum of normal pregnant women was 112.46 pg/ml, in women with pre-eclampsia 50.23 pg/ml and in IUGR alone 175.35 pg/ml. These values were not statistically different from each other. Immunolocalization of VEGF in normal term villous placenta was observed in the syncytiotrophoblast with less intense staining in stromal cells. No qualitative differences in localization of staining between the groups (normal pregnancies, pre-eclampsia, pre-eclampsia plus IUGR, and IUGR) was found. Intensity of staining in stromal cells was also similar in the groups studied. However, intensity of VEGF immunostaining in syncytiotrophoblast was significantly reduced in the three pathological groups (P < 0.02) compared with the control group. These results suggest that reduced VEGF may be responsible, at least in part, for the impaired vascular development which occurs in these conditions. Our results are therefore not consistent with villous placental hypoxia at the time of sample collection.