Background. The Down syndrome is a severe disease without pathogenic therapy. The only possibility to reduce the consequences of disease is prenatal screening and diagnosis. The gold standard in prenatal diagnosis is the conventional banding cytogenetic analysis of fetal cells obtained by invasive procedures. To reduce the complications, in the last years different methods to detect fetal cells or DNA in maternal blood were developed. Aim. The aim of study was to verify the reliability of quantification by immunoprecipitation of methylated fetal DNA in maternal blood in the prenatal diagnosis of 21 trisomy. Method. We analyzed probes from 12 pregnant women (7 with confirmed 21 trisomy pregnancy and 5 with normal pregnancy), with two being rejected for technical considerations. For each probe we carried out: extraction of total DNA (maternal and fetal), DNA fragmentation, immunoprecipitation of methylated DNA, washing, isolation of DNA and qPCR for immunoprecipitated DNA. To highlighting specific methylated regions on fetal 21 chromosome we used eight pairs of specific primers for chromosome 21. Finally we analysed the results of qPCR applying the formula D=- 6.331+0.959XEP4+1.188XEP5+0.424XEP6+0.621XEP7+0.028XEP8+0.387XEP10-0.683XEP11+ 0.897XEP12, where XEPi= fraction value for each marker. Results. In all normal pregnancies the value of D factor was negative concordant with absence of trisomy (100% specificity). In 5 from 6 pregnancies with 21 trisomy the value of D factor was positive, which indicated a high sensibility. However, to a precise estimation of this method is required a larger number of cases that allowing the obtaining of statistically validated results.