In the Netherlands, maternal serum screening for fetal Down’s syndrome (OS) and neural tube defects (NTD) is not supported by the Government as a population-wide study. The number of samples sent to the University Hospital Groningen (AZG) nevertheless increased because of the individual requests of pregnant women in the north of the Netherlands. On 1st October 1990, the existing NTD and DS serum screening programme, using maternal serum alpha-fetoprotein (MSAFP) measurement at the AZG, was extended to incorporate routine measurements of maternal serum human chorionic gonadotropin (MShCG). In the period until December 1991 we calculated the OS and NTD risks in 2282 women. Another 298 women, who had already undergone chorionic villus sampling, only wanted to know their NTD risk. Of the 2282 samples, 59.9% came from outside the AZG and had been sent by 133 different applicants, mainly in the north of the Netherlands. (Chapter 2) The most probable cause for abnormal levels of MSAFP and MShCG in pregnancies associated with OS is a dysfunctional placenta, which causes impaired transp01t of AFP and produces an increased amount of hCG. lt is unlikely that a OS fetus produces less AFP. (Chapter 3) In the period described, 5 of the 6 OS cases were detected, as well as 3 of the 4 cases with a closure defect. We were able to achieve a follow-up of 99.8%. Reliable maternal serum screening is feasible in a strongly decentralized obstetrical organization. It is important to keep serum screening centralized at centres for prenatal diagnosis. (Chapter 4) Maternal serum screening had a major effect on the amniocentesis (AC) rate in women of advanced maternal age. Of all the women of 36 years or older, 34.1 % were screen-positive for OS, but only 41.2% of this group chose to undergo AC. This is of imp01tance in a society were the mean maternal age is steadily increasing. (Chapter 5) Serum screening programmes wrongly determine a high risk of fetal NTD or OS if the concentrations of both MSAFP and MShCG are high. The decision to carry out invasive diagnostic procedures should only be made after extensive ultrasound examination, taking into account the increased risk of an adverse pregnancy outcome. (Chapter 6) Elevation of the MSAFP level in the absence of any fetal abnormalities implies a significantly increased risk of preterm birth or fetal growth retardation. If the MSAFP and MShCG are both elevated, the risk of preterm birth is also slightly elevated. MShCG elevation alone does not indicate a significantly increased risk. An elevated MSAFP is an indication to be extra vigilant during the pregnancy. (Chapter 7) Women are in favour of maternal serum screening but do not consider it acceptable to drop the age indication. In their opinion, the risk involved with serum screening is more significant than the age-related risk, although they did not fully appreciate the possible drawbacks of serum screening. (Chapter 8) From an overview of the Dutch situation concerning ethical, psychosoial, legal and cost-effective aspects, we concluded that these aspects do not form any real obstacles for performing maternal serum screening. It will problably become increasingly problematic if we do not perform this screening. (Chapter 9) Maternal serum screening will become a regular part of obstetrical care and prenatal diagnosis. Uncontrolled growth is already occuning; therefore it is important to reach consensus about quantity and quality requirements for optimal reliability of serum screening.