The α-fetoprotein concentration in the amniotic fluid of 51 fetuses with isolated nuchal edema and normal karyotypes was compared to that of the next 51 patients of comparable gestational age with normal ultrasounds and karyotypes. The mean α-fetoprotein in amniotic fluid was 1.26 ± 0.45 in the nuchal edema group and 1.01 ± 0.3 in controls (t = 3.287, p = 0.002). Acetylcholinesterase evaluation was indicated by abnormally elevated α-fetoprotein in 4% of amniotic fluid samples from the study group and none of the controls. We concluded that α-fetoprotein is higher in amniotic fluid from pregnancies with isolated fetal nuchal edema and normal karyotype. Possible leakage of protein from enlarged cervical lymphatics associated with fetal nuchal edema may explain these fin