Rapid growth and vascularization of the human placenta are characteristic of early pregnancy and are accomplished in an unusually hypoxic environment. Stimulation of placental growth through hypoxia-induced angiogenesis may therefore be of particular importance. We have previously found that several varieties of vascular endothelial growth factor (VEGF) mRNA, including VEGF165, are present in cultured placental fibroblasts. We hypothesized that hypoxia would increase the transcription and translation of VEGF by these cells and provide one mechanism linking placental development with its environment. Placental fibroblasts were grown in aerobic or anaerobic atmospheric conditions for 72 h. By 24 h the oxygen tension of the anaerobic culture media was significantly less than that of the aerobic cultures. RNA was extracted from the cells at 24, 48 and 72 h. Following reverse transcription polymerase chain reaction (RT-PCR) stronger signals for VEGF were always found in the anaerobic cultures and this was confirmed by competitive PCR. mRNA for VEGF165 was represented most strongly but the anaerobic cultures also showed clearly mRNA for VEGF121, VEGF189 and VEGF206. The VEGF protein was also measured in the aerobic and anaerobic culture medium. By 72 h the average concentration of VEGF was significantly higher (P = 0.01) in the anaerobic culture medium. VEGF production is one mechanism through which oxygen supply may influence placental development. Examples of this may include the compensatory placental hypertrophy associated with maternal anaemia and with reproduction at high altitude.