Abnormal amniotic fluid volume can be associated with increased maternal risk as well as perinatal morbidity and mortality. Polyhydramnios is often indicative of fetal, placental or maternal problems. In a large proportion of patients the aetiology of the disorder is unclear. Here we report on a case in which numerous fetal erythroblasts and large quantities of extracellular fetal DNA were found in the peripheral blood of a pregnant woman with idiopathic polyhydramnios bearing a male fetus. Following enrichment of erythroblasts by magnetic separation (MACS) and anti-CD71 antibodies, approximately 45-fold more erythroblasts were determined per mi peripheral maternal blood than in matched controls (231 versus 5). Single cell multiplex polymerase chain reaction (PCR) of individually micromanipulated erythroblasts showed that approximately 122 of these were of fetal origin. The concentration of extracellular fetal circulatory DNA in maternal plasma was determined by real-time quantitative PCR and shown to be almost double that of the control group (749.2 versus 404 fetal genome equivalents per mi maternal plasma). It can be speculated that the increased intrauterine pressure in polyhydramnios leads to an enhanced influx of fetal cells and free extracellular fetal DNA into the maternal circulation. This hypothesis will have to be tested with further cases. Copyright (C) 2000 John Wiley & Sons, Ltd.