Recent publications have reported a relation between a decreased ovarian reserve and Down's syndrome pregnancies. Using the data of a case-control study into risk factors for a Down's syndrome pregnancy, we estimated the usefulness of pre-conceptional basal follicle stimulating hormone (FSH) screening (detection rate, false positive rate, positive and negative likelihood ratio, as well as the loss rate of unaffected pregnancies) to identify Down's syndrome pregnancies. The optimal detection rate of pre-conceptional basal FSH screening for Down's syndrome pregnancies was 14%, corresponding to a false positive rate of 5% and a positive likelihood ratio of 2.8. Incorporation of basal FSH screening into the regimen of first trimester serum screening followed by nuchal translucency measurement would increase the detection rate from 85 to 87%. However, basal FSH screening alone or in combination with other screening methods would cause an unacceptably high loss rate of unaffected pregnancies compared with current screening protocols, indicating that routine pre-conception basal FSH screening would not be useful to identify women at risk for a Down's syndrome pregnancy. However, when elevated basal FSH concentrations are diagnosed during subfertility evaluation, an elevated risk for a Down's syndrome pregnancy could be discussed with women who become pregnant.