Patterns of fetoplacental angiogenesis vary during gestation and in association with certain pregnancy pathologies. In a set of three linked reviews, we provide a survey of current knowledge about the molecular regulation, cellular players, qualitative and quantitative morphological features of the vascularization of human placental villi. Here, an account is given of the role played by hypoxia-inducible factor in mediating the effects of oxygen on production of growth factor ligands and receptors which regulate angiogenesis and vessel maturation. However, it should be noted that, for the human placenta early in gestation, the normal (i.e. physiological) partial pressure of O(2)is low but this does not mean that the tissue is hypoxic. Thus, the mechanisms of regulating angiogenic growth factor production may differ at this time in comparison to those found later in gestation or in other tissues or organs. The vasculature in the placenta is plastic and changes markedly as gestation progresses. This is controlled by the complex interplay between physical factors and chemical factors including oxygen, growth factors and growth inhibitors. The companion reviews describe morphological features of normal and pathological development of the human placenta in the context of the factors discussed here.