Objective: To investigate the association between adverse perinatal outcomes and abnormal elevations of serum marker levels (alpha-fetoprotein [AFP] and free beta-hCG) or a false-positive screen for Down syndrome. Methods: Pregnancy outcome information was available for 5885 Taiwanese women under 35 years of age who had second-trimester maternal serum screening for Down syndrome, using AFP and free beta-hCG, and delivered a chromosomally normal fetus. Those with AFP at least 2.0 multiples of the median (MoM), free beta-hCG at least 2.5 MoM, or a false-positive screen (risk ratio at least 1:270) were identified, and the risk for adverse perinatal outcome was assessed. Results: A serum AFP level at least 2.0 MoM (n = 176, 3.0%) was significantly associated with the occurrence of preterm delivery, low Apgar scores, small-for-gestational-age infants, low birth weight or very low birth weight, fetal death, premature rupture of membranes, oligohydramnios, and a higher incidence of perinatal mortality. A serum free beta-hCG level at least 2.5 MoM (n = 416, 7.1%) was significantly associated with low birth weight, an abnormally adherent placenta, and the occurrence of meconium-stained amniotic fluid. A higher incidence of fetal structural anomalies other than neural tube or abdominal wall defects, large-for-gestational-age infants, and postpartum hemorrhage was observed for a calculated risk of at least 1:270 (n = 311, 5.3%) independent of the other biochemical markers. Conclusion: Asian women with unexplained elevations of serum AFP or free beta-hCG, or a false-positive screen for Down syndrome are at increased risk for various adverse perinatal outcomes. Careful fetal ultrasound examination and thoughtful strategy for perinatal management are warranted for these patients. (C) 1997 by The American College of Obstetricians and Gynecologists.