OBJECTIVE: Our objective was to determine if the low birth weight associated with unexplained elevations of midtrimester maternal serum a-fetoprotein levels is due to prematurity or to fetal growth retardation. STUDY DESIGN: Rates of preterm delivery and fetal growth retardation were analyzed according to incremental maternal serum α-fetoprotein levels in 5555 women, predominantly white, who were screened for neural tube defects (group 1) and 843 women, predominantly black, with risk factors for low birth weight (group 2). Statistical methods included χ2, t tests, analysis of variance, and regression analysis. RESULTS: In both groups increasing levels of maternal serum α-fetoprotein are significantly associated with preterm delivery but not with fetal growth retardation. The preterm delivery rate increased in each group from 8% at levels <0.5 multiples of the median to 18.1% (p < 0.001) at levels ≥2.5 multiples of the median in group 1 and 28.1% (p = 0.01) in group 2. CONCLUSIONS: Women with unexplained elevations of maternal serum α-fetoprotein are at increased risk for preterm delivery but not fetal growth retardation. Because of the wide availability of maternal serum α-fetoprotein screening, women at increased risk for preterm delivery can be identified in the midtrimester of pregnancy. © 1992, Mosby. All rights reserved.