The maternal serum alpha-fetoprotein (AFP) in 6161 women in routine pregnancy [2771 in a hospital obstetric clinic (group 1) and 3390 in private practices (group 2)] was studied. Group 1 studies enabled the delineation of the normal range of serum AFP, whereas group 2 represented a true screening experience. In group 2, 39 (2.5%) of 1566 women at 16 to 18 weeks' gestation had raised (2.5 times the median or more) serum AFP. Of these 39 women, 3 (7.8%) had neural tube defects (NTDs), 6 (15.4%) had multiple pregnancies, 1 (2.6%) had congenital nephrosis, 7 (17.9%) had spontaneous abortions, 7 (17.9%) had miscellaneous associated factors, and 15 (38.5%) had raised serum AFP for no obvious reason. Only 16 (1%) women had "unnecessary" amniocenteses. None of these aborted subsequently. Analysis of the combined data showed that NTDs were detectable in 87.5% of patients-all 6 with anencephaly and 1 of 2 with spina bifida (1 spina bifida lesion closed); multiple pregnancy was determined in 45% (18/40 cases), and spontaneous abortion ensued in 14.5%. In group 1 a raised serum AFP was associated with a host of complications in 77.3% of the women. Low AFP values had associated complications in 72.2% of cases. Maternal serum AFP screening represents another potentially important tool for early detection of high-risk pregnancy.