Measurement of amniotic fluid concentrations of alpha1-fetoprotein has been proposed as a potentially important screening test of fetal well-being. Because maternal serum is more easily obtainable, the present study was performed to determine if there is a definable normal pattern of maternal serum alpha1-fetoprotein levels during gestation. Sequential alpha1-fetoprotein determinations were performed throughout gestation on the serums of 151 women having apparently normal pregnancies. Before 13 weeks, all samples contained less than 20 nanograms of alpha1-fetoprotein per milliliter of serum, and in 12.5 per cent of normal pregnancies, alpha1-fetoprotein was still undetectable as late as 21 weeks of gestation. One normal term delivery followed a negative alpha1-fetoprotein determination at the 24th week of pregnancy. Beyond the 21st week of pregnancy, there was a wide range of normal absolute values noted between women at the same stage of pregnancy. Moreover, wide fluctuations in maternal serum concentrations of alpha1-fetoprotein were observed from point to point in specimens from individual women studied longitudinally throughout gestation. The distribution of alpha1-fetoprotein concentrations at each stage of pregnancy was skewed. We conclude that studies of maternal serum alpha1-fetoprotein concentrations are likely to be more meaningful from a diagnostic point of view prior to 21 weeks of gestation, when the range of circulating maternal alpha1-fetroportein values is relatively small. Undetectable maternal serum alpha1-fetoprotein as late as the 24th week of pregnancy is compatible witha viable conceptus. Because unexplained and marked elevations of maternal alpha1-fetoprotein may occur, particularly in the third trimester, it would appear inappropriate to base clinical decision on maternal serum alpha1-fetoprotein measurements alone, and such decisions certainly should not be taken after only single maternal serum alpha1-fetoprotein measurements. Finally, no correlation was found between maternal alpha1-fetoprotein concentrations near term and the birth weight of the infant.