The administration of phenobarbital to pregnant women before delivery has been thought to decrease the frequency of intracranial hemorrhage in preterm infants. To evaluate this potential neuroprotective therapy further, we determined the effect of antenatal administration of phenobarbital on the frequency of neonatal intracranial hemorrhage and early death. Women who were 24 to 33 weeks pregnant and who were expected to deliver their infants within 24 hours were randomly assigned to receive either intravenous phenobarbital (10 mg/kg body weight) or placebo, followed by maintenance doses until delivery or 34 wks gestation. Infants less than 34 wks at birth underwent serial cranial ultrasonography to detect the presence of intracranial hemorrhage. The sample size of 1038 pregnancies was based on an intracranial hemorrhage rate of 20 percent in the placebo and less than 12 percent in the phenobarbital group; 90 percent power; a 5 percent two-tailed type 1 error; and an 8 percent noncompliance rate. The twin with the highest grade of intracranial hemorrhage was included.