We used concanavalin A crossed-line affinity immunoelectrophoresis to determine the percentage of concanavalin A nonreactive alpha-fetoprotein in amniotic fluid samples from pregnancies with normal and abnormal fetuses. In 167 samples from pregnancies with a normal outcome and normal values for total alpha-fetoprotein concentration in amniotic fluid the percentage decreased from a median value of 27.4% in the 13th week to 8.5% in the 21st week of gestation, and a statistically significant (p < 0.001) average decrease of 1.7% per week was found from the 14th to the 19th week. A similar average decrease (2.2%) was found in 22 pregnancies from which two or more samples were obtained. The clinical significance of this decrease is discussed. Of 108 samples from patients with above-normal values for total alpha-fetoprotein and a normal outcome, seven had a total alpha-fetoprotein above recommended cut-off values, and only one of these had a low percentage of concanavalin A nonreactive alpha-fetoprotein. In contrast, for all 27 samples from pregnancies with a severe fetal malformation this percentage was low, even in one case where the total alpha-fetoprotein concentration was below the recommended cut-off value.