In order to gain more insight into the association between alpha-fetoprotein (AFP) and fetal chromosomal disorders, especially Down's syndrome, we measured AFP in fetal serum, amniotic fluid, and maternal serum at cordocentesis. We compared the concentration and gradient of AFP in these three compartments. Our data confirm earlier findings on second-trimester fetal serum AFP concentration. The results indicate that low maternal serum AFP in pregnancies with fetal chromosomal disorders could result from an impaired fetal kidney function as well as from impaired membrane or placental passage of AFP, rather than from reduced fetal AFP production.