The incidence and diagnostic accuracy of the lemon and cerebellar ultrasonographic markers, as well as head size and ventriculomegaly, were evaluated in a study of 1561 patients at high risk for fetal neural tube defects. In the 130 fetuses with open spina bifida there was a relationship between gestational age and the presence of each of these markers. The lemon sign was present in 98% of fetuses at less than or equal to 24 weeks' gestation but in only 13% of those at greater than 24 weeks' gestation. Cerebellar abnormalities were present in 95% of fetuses irrespective of gestation; however, the cerebellar abnormality at less than or equal to 24 weeks' gestation was predominantly the banana sign (72%) whereas at gestations greater than 24 weeks it was cerebellar "absence" (81%). Both growth retardation and cerebral ventriculomegaly significantly worsened with gestation while the head circumference remained disproportionately small throughout gestation. On the basis of these data, a new approach is proposed for the investigation of patients at high risk for fetal open spina bifida.