The objective of this study was to determine if an ultra-sound examination, when performed in the third trimester immediately preceding delivery, is useful in predicting outcome in infants with a myelomeningocele. A retrospective review was undertaken of prenatal ultrasound records arid pediatric outcome data on fetuses with isolated myelomeningocele referred to our institution after 28 weeks' gestation during a three-year period. Macrocephaly proved to be the one antenatal ultrasound finding that most correlated with later poor outcomes in infants with myelomeningocele. Macrocephalic fetuses had a longer mean hospital stay after birth and were more likely to have significant respiratory and feeding difficulties. No fetus with macrocephaly had a normal mental score, and all had severe motor deficits on later follow-up testing. The ultrasound diagnosis of macrocephaly identified a group of fetuses with myelomeningocele, who were at highest risk of neonatal problems and developmental delay. Cesarean delivery and aggressive medical treatment of complications did not improve the outcome in these infants. This finding will be useful when counseling patients regarding route of delivery and in pediatric decisions regarding treatment of complications.