A total of 12,084 patients participated in a maternal serum alpha-fetoprotein (AFP) screening program in central North Carolina between July 1, 1978, and June 30, 1982. Fifteen open neural tube defects were detected and three others were missed, resulting in a detection rate of 83%. With a cutoff of 2.5 times the normal median, 3.7% of patients screened had a single maternal serum AFP elevation, 2.1% had two successive elevations, and 1.2% became candidates for amniocentesis. Of those patients offered amniocentesis, one in 10 was found to have a fetus with a neural tube defect. No normal fetuses have been aborted. Patients with maternal serum AFP elevations were shown to have a substantially increased risk of fetal loss. Low maternal serum AFP levels were also a significant finding and led to recognition of less advanced gestational age, fetal death, or molar pregnancy in a number of cases.