The value of measuring inhibin-A (asA dimer) with human chorionic gonadotrophin (total or the sub-units free a-hCG and free P-hCG separately), alpha-fetoprotein (AFP), and unconjugated oestriol (uE,) was examined to determine the effect on the performance of serum screening for Down's syndrome between 15 and 22 weeks of pregnancy. The study was based on stored serum samples from 77 Down's syndrome singleton pregnancies and 385 unaffected singleton pregnancies, matched for maternal age, gestational age, and duration of storage of the sample, supplemented by data from 970 white women with unaffected pregnancies. Inhibin-A was elevated in the serum of women with Down's syndrome pregnancies with a median of 1.79 multiples of the median (MOM). Using the four serum markers AFP, uE,, total hCG, and inhibin-A, in addition to maternal age, 70 per cent of Down's syndrome pregnancies were detected for a 5 per cent false-positive rate compared with 59 per cent with the conventional triple test (AFP, uE,, and total hCG with maternal age). If the estimate of gestational age were based on an ultrasound scan examination, the detection rate would be 77 per cent [95 per cent confidence interval (CI) 69-85 per cent] using the four serum markers including inhibin-A, compared with 67 per cent with the triple test or 79 per cent (95 per cent CI 71-87 per cent) if marker values were adjusted for maternal weight. If the detection rate were kept at 70 per cent and the gestational age were estimated by an ultrasound scan examination, the four-marker test would reduce the false-positive rate from 6.1 per cent using the triple test to 2.9 per cent. The results were virtually the same if free 8-hCG was used instead of total hCG. The inhibin-A-based four-marker test is the most effective method of prenatal screening for Down's syndrome suitable for routine use. If the extra cost required t o carry out the inhibin-A test were less than about E3 per woman screened, the four-marker test including inhibin-A would be financially cost-effective.