A dual polymerase chain reaction (PCR) technique is developed which enables the detection of one part male DNA in 25,000 parts female DNA. The technique amplifies a part of the X-Y homologous amelogenin gene in which the Y counterpart has a 189 bp deletion within one of the introns. This deletion has made it possible to identify individual X and Y counterparts based on the difference in size between them. None of the 18 pregnant women studied showed a positive Y-signal although eight of them bear male fetuses excluding the presence of fetal cells at one in 25,000 maternal cells. The results presented here show that a sensitivity of greater than one in 25,000 is required for detection of fetal genetic disease using maternal peripheral blood.