We describe the recovery and identification of fetal nucleated red cells from maternal blood and the application of this procedure to the prenatal diagnosis of hemoglobinopathies by immunocyto-chemistry. Our efforts have been based on the assumption that specific antibodies against globin chains should reveal the presence of abnormal hemoglobins (HbS) or the failure to synthesize a particular chain (thalassemias). Since the test is based on the detection of polypeptides, both nucleated and non-nucleated red cells are suitable for the implementation of the diagnosis, provided that the cells of fetal origin can be identified with absolute certainty. For this purpose we have produced a series of antibodies against embryonic (anti ζ), fetal and adult globin chains (α, ß, ß6-glu, specific for HbA in the presence of HbS, ß6-val, specific for HbS) and human Carbonic Anhydrase B. We have successfully used the immunostaining to confirm the absence of α-globin (and the presence of ζ and Y chains) in the erythroblasts and red cells of fetuses homozygous for α°-thalassemia. Until now we have not observed any discrepancy between diagnoses carried out by immunocytochemistry and DNA analysis. The specific anti ßA and anti ßS antibodies have been able to identify, by double immunofluorescence applied to artificial cell mixtures, erythrocytes homozygous or heterozygous for hemoglobins A and S. We are now experimenting the use of these antibodies in the prenatal diagnosis of sickle-cell anemia.