Five cases of trisomy 16 confined to the placenta have been detected by invasive procedures (amniocentesis and chorionic villus sampling) after high-risk results for Down syndrome and neural tube defects in a maternal serum screening programme of 6614 consecutive cases. All five pregnancies displayed unusually elevated levels of human chorionic gonadotropin and four out of five also had raised alpha-fetoprotein values. No structural malformation was present but all five pregnancies were complicated by fetal growth retardation, and one by intrauterine death. From our results, we suggest that both amniocentesis and chorionic villus sampling should be considered in the management of cases with high mid-trimester levels of these analytes.