Plasma adrenomedullin concentrations are increased in the fetal circulation in acute and chronic hypoxic conditions. The effect of hypoxia in regulating adrenomedullin synthesis and secretion was investigated in human placental trophoblast cells.Human trophoblast cells obtained from term placentas (n=7) were cultured in hypoxic condition (3% oxygen). Cytotrophoblast cells were cultured for up to 48h and syncytiotrophoblasts for 2, 8 and 24h. Changes in adrenomedullin output compared to normoxic conditions were measured by radioimmunoassay. Protein expression was evaluated with Western blot and immunocytochemistry.Hypoxia induced a time-dependent increase in adrenomedullin output and protein expression by placental trophoblast cells.Hypoxia regulates adrenomedullin secretion and expression by human placenta, thereby promoting increased adrenomedullin concentration in the fetal circulation in clinical circumstances characterized by reduced oxygen levels.