Loading doses of 15 to 20 mg per kilogram of both phenobarbital and phenytoin, administered intravenously, are necessary in the newborn to achieve rapid therapeutic plasma anticonvulsant levels. Maintenance doses of 3 to 4 mg per kilogram of both agents will maintain therapeutic levels. Phenytoin is, however, not predictably absorbed by the oral route. Brain:plasma ratios were 0.71 +/- 0.21 for phenobarbital and 1.28 +/- 0.32 for phenytoin, which are in general agreement with reported adult values. The brain:plasma ratio of phenobarbital increased with gestational age. Phenytoin was found in higher concentration in gray matter, whereas phenobarbital was equally distributed between gray and white matter.