Recent retrospective studies have shown a correlation between low maternal serum AFP levels and the presence of a fetus with an autosomal trisomy. The amniotic fluid AFP levels in these pregnancies tend to be decreased. A possible explanation for the low maternal serum AFP is that the trisomic fetus produces less AFP and/or impairs placental transport of AFP. Alternatively, the AFP in maternal serum might represent endogenous production in response to a fetal signal (reactivation of the previously repressed AFP gene) and the defective trisomic fetus is unable to provide an adequate signal. This study was undertaken to examine the contribution of the maternal liver to the AFP that appears in the maternal serum during pregnancy. Total RNA was isolated from the livers of pregnant, non-pregnant, and fetal mice. Northern blots were prepared and probed with cDNA for mouse AFP and rat albumin mRNA. The albumin probe hybridized well with all samples whereas the AFP probe hybridized only with the fetal liver RNA. The results are consistent with the widely held notion that maternal serum AFP is entirely of fetal origin. Decreased maternal serum AFP associated with a trisomic fetus may contribute to an increased risk for fetal demise, pregnancy less, or other adverse outcome.