The growing acceptance of maternal serum α-fetoprotein (MSAFP) screening as a vital part of obstetrical care coupled with the marketing of commercial AFP kits has encouraged clinical laboratories to begin the business of MS AFP testing. The tendency among laboratories has been to approach prenatal MS AFP screening as a diagnostic process. Understandably, the diagnostic manner is familiar to all laboratories, yet there is a distinction between diagnosis and screening. Screening results in the identification of an increased-risk patient subgroup that contains most, if not all, affected cases. To achieve an optimal program of MS AFP screening requires coordination of several components centered around the laboratory. Through preliminary assay set-up and continuous monitoring of performance, to effective communication to educate about screening and inform of ret risk and recommend tests for diagnosis, and finally to evaluate pregnancy outcome as a measurement of efficient detection, the laboratory must function within the screening protocol. We will focus on the laboratory role throughout the MS AFP screening protocol with emphasis on the adjustments needed for a screening approach. The laboratory that operates outside a screening protocol not only undermines the reliability of the test but also contributes to ambivalence about MSAFP screening for fetal defects.