The clinical efficacy of rocket immunoelectrophoresis (RIE) and radioimmunoassay (RIA) methods for the measurement of amniotic fluid alpha-fetoprotein (AFP) were compared in separate series of over 1,000 pregnancies each. Using a mean +3 SD limit, 21 of 1,414 pregnancies monitored with RIE and 21 of 1,006 monitored with RIA were interpreted as having borderline elevated values. Five of the elevated AFP values in each series represented abnormal fetuses. No neural tube defects went undetected, although one was recognized only with ultrasound. Only two of seven abnormal fetuses had a family history of neural tube defects, indicating that maternal serum AFP measurement is an important preventive measure in pregnancies that are not recognized as at high risk. The data support the use of commercially available RIA kits for amniotic fluid AFP measurement and suggest a protocol for management of elevated values.