As the number of women undergoing invasive prenatal diagnosis for cytogenetic, molecular, or biochemical testing is increasing, the development of new non-invasive methods of analyzing fetal cells is imperative. We have analyzed blood from 27 pregnant women (gestational age of 10-11 weeks) by the polymerase chain reaction (PCR) with oligonucleotide primers specific for Y sequences. The sensitivity of our assay, which did not include a step for fetal cell selection prior to PCR analysis, was 45% and the specificity was 89%. A review of the published studies of non-invasive prenatal diagnosis is provided. We conclude from our results and those of others that it is feasible to amplify fetal-specific sequences from maternal blood. However, techniques such as fluorescence-activated or magnetic-activated cell sorting of the maternal blood, as used in other studies, are necessary to enrich for fetal cells prior to analysis. With further improvements of these techniques, it is likely that fetal cell typing from maternal blood will be a feasible method of non-invasive prenatal diagnosis.