Advances in prenatal diagnosis have generally focused on the use of noninvasive methods of detecting chromosomally abnormal fetuses. Certain ultrasonographic findings, such as femur shortening, humeral shortening, thickened nuchal fold, and structural anomalies, have a positive predictive value for the diagnosis of trisomy 21. Maternal serum screening for proteins present in abnormally high or low levels in trisomy 21 pregnancies is an area of active investigation. Specific substances of interest include α-fetoprotein, β-human chorionic gonadotropin, unconjugated estriol, and urea-resistant neutrophil alkaline phosphatase. Fetal nucleated erythrocytes and trophoblast cells have been isolated from maternal blood. These methods hold promise for identification of fetal aneuploidy in all pregnant women, independent of maternal age.