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To evaluate maternal serum screening for trisomy 21 (MSS) in Flanders between 1992 and 2002.Data of a large database on the results of MSS, nuchal translucency (NT) and pregnancy outcome were analysed retrospectively.Despite an excellent performance of second trimester MSS at a maternal ageor = 35 years (94.4% detection rate (DR) of trisomy 21 at a false positive rate (FPR) of 22.4%), the proportion of patients above 35 years of age in the study population was significantly lower than in the Flemish general pregnant population (5.5% versus 8.9%, P0.001). In the population screened by MSS and NT, the DR of second trimester MSS at a 5% FPR was 44.4%, which was lower than 66.6% in the population screened by MSS without NT. When nine trisomy 21-affected pregnancies were compared to 3265 normal pregnancies, the mean NT-MoM values were not significantly different (1.16 +/- 0.89 versus 1.00 +/- 0.46, P0.05). Both the findings comply to a sequential screening practice where second trimester MSS is only performed after a normal measurement of NT in the first trimester.In Flanders, the uptake of second trimester maternal serum screening is low in women aged 35 years or more. Its screening performance decreased after the introduction of sequential screening.