Ultrasound measurements of 15 fetuses with trisomy 21 detected during the 17th week of gestation were matched retrospectively to those of 45 normal controls. We compared nine standard ultrasound measurements of the fetal head, abdomen, and femur in these two groups. The fetuses with trisomy 21 had significantly shorter mean femur lengths, narrower occipitofrontal diameters, and increased biparietal diameter (BPD)/femur length and abdominal circumference/femur length ratios. An increased BPD/femur length ratio was the ultrasound finding that best predicted a fetus with Down syndrome. A BPD/femur length ratio of 1.80 or higher was 40% sensitive and 97.8% specific in predicting Down syndrome, and had a false-positive rate of only 2.2%. An increased second-trimester BPD/femur length ratio measured by ultrasound may prove beneficial as an additional screening test for Down syndrome.