Our laboratory is a leading pioneer in the enrichment of fetal cells from maternal blood with the aim of developing a non-invasive risk free form of prenatal diagnosis. By using the then novel Magnetic Activated Cell Sorting (MACS) we were among the first to detect fetal aneuploidies. The efficacy of this methodology is currently being explored in the large scale so-called, NIFTY study conducted under the auspices of the NIH, in which our group is participating. We have extended the scope of these investigations by analysing single micromanipulated erythroblasts by single cell PCR. These studies have shown that fetal genetic loci such as sex and rhesus D status can be identified with great reliability non-invasively. This analysis also irrevocably demonstrated that a large proportion of the erythroblasts in maternal circulation are of fetal origin. This aspect has now been incorporated into the next phase of the NIH study. Recent research from our laboratory has indicated that the traffic of fetal cells into the maternal periphery is significantly enhanced in preeclamptic pregnancies. We have now investigated whether this perturbation takes place early in pregnancy prior to the onset of disease symptoms, by performing a prospective study in which close to 100 pregnant women were recruited at around 20 weeks of gestation. By correlating the number of enriched erythroblasts with subsequent pregnancy outcome, we were able to show that the traffic of fetal cells was indeed significantly elevated in those pregnancies which developed preeclampsia, but not those which were affected by fetal growth retardation. We have also explored the new finding of free fetal DNA in maternal plasma. By the use of sensitive quantitative PCR we were recently able to show that the levels of this circulatory fetal DNA are elevated in pregnancies with certain aneuploidies, thereby opening the prospect of a new additional screening tool.