This study investigates whether first-trimester screening for trisomy 21 by fetal nuchal translucency thickness preferentially identifies those fetuses destined to die in utero and examines the potential impact of such a method of screening on the live birth incidence of trisomy 21. In 70 pregnancies, trisomy 21 was diagnosed at 12 (range 11-14) weeks of gestation and the parents opted for elective termination which was carried out at 14 (12-20) weeks. In all cases, viability was established by ultrasound scan at the time of chorion villus sampling (CVS) and just before termination of pregnancy. Eight (11.4%) fetuses died in the interval between CVS and termination of pregnancy and this rate of lethality was higher than the 6.9% estimated rate for an unselected population of trisomy 21 fetuses. This 4.5% increase may, in part, be attributed to the effects of CVS and may also be due to patient selection on the basis of increased nuchal translucency. The rate of lethality increased with translucency thickness from 5.3% for those with translucency of 1-3 mm to 23.5% for translucency of > 7 mm. In trisomy 21, the rate of intrauterine lethality is associated with nuchal translucency thickness. Nevertheless, a policy of screening by maternal age and fetal nuchal translucency followed by selective termination of affected fetuses would still result in a more than 70% reduction in the live birth incidence of trisomy 21.