A subnormal maternal serum alpha-fetoprotein level associated with elevated alpha-fetoprotein level in amniotic fluid was found in a case of trisomy 21 combined with esophageal atresia in a fetus at 36 + 5 weeks of gestation. The significance of this observation is discussed in view of the possible biologic mechanisms resulting in maternal serum alpha-fetoprotein reduction in cases of fetal autosomal trisomies. The most likely hypotheses seem to be a reduced fetal alpha-fetoprotein production and/or an alteration of the placental regulation of the alpha-fetoprotein transfer from fetal to maternal blood via the placenta.