There is a certain degree of foetal-maternal transfusion in every pregnancy. The possibilities for using intact foetal cells extracted from maternal blood for prenatal diagnosis are limited. Recently real-time polymerase chain reaction (PCR) techniques have allowed the identification and quantification of foetal DNA in the maternal blood. Foetal sex determination with Y-chromosome-PCR has been found to have a specificity of 100%. The sensitivity is 96% but increases with gestational age, so that from 10 weeks onwards the sensitivity approaches 100%. In the case of X-linked diseases, this technique can reduce invasive prenatal diagnosis by 50%. In the case of a foetus with an elevated risk for congenital adrenal hyperplasia, early non-invasive foetal sexing can also shorten the period of maternal dexamethasone use so as to prevent virilisation in the female foetus. Early second trimester non-invasive foetal RhD genotyping with an RhD-PCR has a sensitivity and specificity of 100% each. Therefore in the future, anti-D immunoprophylaxis will be superfluous in RhD-negative women with an RhD-negative foetus. Theoretically all new and paternal inherited disorders with a known gene defect can be detected in maternal plasma. Some examples have already been described. Recently published small scale studies describe elevated concentrations of free foetal DNA in maternal plasma in (threatening) preterm labour, pre-eclampsia and aneuploidy. Large-scale studies are necessary to demonstrate the value of these findings.