Down's syndrome (DS) is the commonest single cause of severe mental retardation in children. It can be diagnosed antenatally by chorionic villus sampling (CVS) or amniocentesis followed by karyotyping. At one time the sole indication for these invasive procedures was maternal age: typically women above age 35. However, this led to the detection of only some 30% of cases of DS at best. In the past ten years a series of biochemical and other abnormalities have been noted in Down's pregnancies and these form the basis for new screening programmes. The most familiar of the biochemical abnormalities are elevated levels of maternal serum human chorionic gonadotrophin (hCG), and reduced levels of α‐fetoprotein (AFP) and oestriol (E3). Changes are also noted in a number of other fetoplacental products. The underlying mechanism of these changes is unknown: suggestions include the possibility that a Down's syndrome pregnancy is relatively ‘immature’, or that there is a fetal–placental i