To determine the status of maternal serum alpha-fetoprotein screening for fetal Down syndrome in the United States, we surveyed member laboratories in the External Quality Assessment Scheme for Pregnancy alpha-Fetoprotein in the spring of 1988. Of the 123 member laboratories that provide screening services, 109 responded. The 109 laboratories screened 586,000 pregnancies annually, and 96 provided interpretations for risk of fetal Down syndrome, accounting for 534,000 pregnancies. Numbers of women screened annually per laboratory ranged from less than 200 to greater than 27,000 (median 3000). A total of 85 of the 96 laboratories used a combination of the maternal serum alpha-fetoprotein cut-off. Ultrasonographic gestational dating was used for the initial interpretation in 25% of the screened pregnancies. The median initial positive rate (the number of women initially classified as being at increased risk) was 3.7% overall, and smaller laboratories were more likely either to have outlying initial positive rates or to be unable to provide such rates. Median initial positive rates were lower for enzyme immunoassay kits than for radioimmunoassay kits (3.0% versus 4.8%). These results indicate that, whereas most laboratories appear to perform satisfactorily in screening for fetal Down syndrome, some laboratories appear to perform satisfactorily in screening for fetal Down syndrome, some laboratories need to refine their methods of assigning risk and others need to develop mechanisms to document initial positive rates and, when appropriate, to analyze the cause of outlying initial positive rates. This survey, combined with information from nonsurveyed laboratories known to screen for fetal Down syndrome, allows an estimation that 1 million pregnancies annually were provided with fetal Down syndrome interpretations in the United States in mid-1988.