Pregnancy outcome was followed prospectively in women showing maternal serum alpha-fetoprotein values less than 0.4 multiple of the median. Using a radioimmunoassay later shown by others to produce a disproportionate number of low values, we nonetheless detected all three cases of autosomal trisomy (+18, +18, +21) at amniocentesis in 1531 women screened. Although two fetal losses and two autosomal trisomies (trisomy 18) occurred among a subgroup of only 15 women having two values less than 0.25 multiple of the median, fetal losses were in general far less frequent among the 99 women with at least one maternal serum alpha-fetoprotein value less than 0.4 multiple of the median than among women in previous reports. Comparing women with maternal serum alpha-fetoprotein values less than 0.4 multiple of the median against those with normal values (0.4 to 2.49 multiples of the median) also revealed no significant differences with respect to presence or absence of a variety of antepartum or intrapartum complications. Birth weight, gestational age, arterial cord pH, and Apgar scores also failed to differ significantly (one-way analysis of variance, p greater than 0.05). Women with a viable pregnancy who show low maternal serum alpha-fetoprotein values have a more favorable prognosis than previously claimed.