We describe a potential screening method for the second trimester detection of the fetus with Down syndrome by the use of standard sonographic biometry. Retrospective assessment of the biparietal diameter, femur length, and biparietal diameter/femur length ratio in 55 fetuses with Down syndrome and 544 control fetuses was performed at two medical centers. Adequate numbers of cases and controls were available to permit statistically significant comparisons between the groups at 15 to 23 weeks' gestation. Fetuses with Down syndrome displayed no statistically significant differences in the cephalic index or the biparietal diameter compared with controls at a given gestational age. Significant femur length shortening was observed, but the greatest statistical difference was noted for the biparietal diameter/femur length ratio. This ratio was found to decrease with gestational age in the normal population and was consistently elevated in the Down syndrome population (compared with control) throughout the second trimester. With a cutoff value of 1.5 SD above the normal population mean for the biparietal diameter/femur length ratio, 50% to 70% of fetuses with Down syndrome could be identified in 6% of the total population (p less than 0.0001). This preliminary study suggests that the biparietal diameter/femur length ratio may prove superior to current Down syndrome screening methods and, as a third independent variable, may significantly enhance the sensitivity and specificity of combined maternal age/maternal serum alpha-fetoprotein screening modalities.