Maternal serum screening for alpha-fetoprotein, initially as an indicator of open neural tube defects and more recently combined with other pregnancy-specific markers as an indicator of Down's syndrome, is an established part of prenatal testing. Recent work has focused on the role of folic acid in the primary prevention of neural tube defects and on the search for a genetic component in the aetiology of neural tube defects. Potential new markers of Down's syndrome have been identified in maternal serum and urine. Nuchal translucency measurements by ultrasound and the identification of appropriate maternal serum markers in the first trimester offer the prospect of screening earlier in pregnancy.