The aim of this study was to evaluate the feasibility of first-trimester biochemical screening for trisomy 18, by using pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (hCG) in combination with maternal age. Maternal serum levels of PAPP-A and free beta-hCG were assayed retrospectively in stored sera from 323 singleton pregnancies at 8-13 weeks' gestation. These samples included 23 trisomy 18 pregnancies and 300 unaffected controls, diagnosed either at chorionic villus sampling or at mid-trimester amniocentesis. The median MOM in affected pregnancies was 0.25 for PAPP-A and 0.34 for free beta-hCG. Statistically significant reductions were found in the mean levels of both PAPP-A (t test: P < 0.000001) and free beta-hCG (p < 0.000001) in trisomy 18 affected pregnancies when compared with the unaffected samples. Screening for trisomy 18 using a combination of maternal age, PAPP-A and free beta-hCG would achieve a detection rate of 76.6 per cent for a false-positive rate of 0.5 per cent. These results suggest that first-trimester biochemical screening for trisomy 18 might be possible. Further investigations in a general population are needed before introducing such screening into clinical practice.