An association between low maternal serum alpha-fetoprotein (MSAFP) and fetal trisomy has now been thoroughly documented. The mechanisms resulting in low MSAFP are still unclear. In order to determine whether the low values of MSAFP in autosomal trisomies are associated with smaller fetal weights, we compared 11 fetuses with Down syndrome (trisomy 21), 4 with trisomy 18, with 45 normal fetuses. All of them are aborted in the second trimester of pregnancy. No significant difference in the weight distribution between fetuses with Down syndrome and control fetuses was found. In contrast, as compared with the control fetuses, fetuses with trisomy 18 had a significant lower weight distribution. The mean value of MSAFP was 0.72 +/- 0.26 MoM for those with Down syndrome and 0.51 +/- 0.33 MoM for fetuses with trisomy 18; both results being significantly lower than that of normal control (1.01 +/- 0.28). The mean value of amniotic fluid AFP was 0.63 +/- 0.23 MoM for fetuses with Down syndrome. This value was significantly lower than those of the fetuses with trisomy 18 and normal controls (1.02 +/- 0.09 and 1.02 +/- 0.30). A linear relationship between MSAFP and fetal weight was found in normal fetuses at a given gestational age but was not found in trisomy pregnancy. Fetal weight cannot be used to explain the reason for low MSAFP in Down syndrome pregnancy but may partially account for the lower levels noted in fetuses with trisomy 18.