Cranial and cerebellar ultrasound markers of open spina bifida were evaluated in a prospective screening study of 436 pregnancies at high risk for this fetal abnormality. Twenty-six fetuses with open spina bifida were diagnosed. Values below the fifth percentile for gestation were found for biparietal diameter (BPD) in 17 fetuses (62%) and for head circumference in nine (35%). The anterior horn of the lateral cerebral ventricle/hemisphere ratio was above the 95th percentile in 11 (42%), and there was ventriculomegaly of the posterior horn of the lateral ventricle in 14 (54%). Scalloping of the frontal bones, referred to as the "lemon sign," was present in all 26 cases and also in five (1%) of the structurally normal fetuses. A cerebellar abnormality was found in 25 cases (96%). In nine fetuses (35%), the cerebellum was absent, and in 16 cases (62%), the cerebellar hemispheres curved anteriorly, producing the "banana sign." The predictive ability of each ultrasound marker to detect open spina bifida was evaluated by measuring the sensitivity, specificity, and predictive value of a positive and negative test. These findings demonstrated that certain cranial and cerebellar markers, in particular the lemon sign and the banana sign or absent cerebellum, are consistent features of open spina bifida and are likely to improve the diagnostic accuracy of ultrasonography in the evaluation of pregnancies at high risk for this fetal abnormality.