Phenobarbital sodium has been used in anticonvulsant concentrations (15 to 40 micrograms/mL serum) in premature newborns in attempts to prevent periventricular and intraventricular hemorrhages. Although its clinical usefulness in this regard is controversial, phenobarbital treatment has been shown to reduce periventricular and intraventricular hemorrhages after hypertensive insult in newborn beagles. In this study cerebral blood flow values in steady state and during phenylephrine-induced hypertension with and without phenobarbital pretreatment were measured in newborn beagles. At anticonvulsant dosage, phenobarbital sodium decreased mean arterial blood pressure transiently during steady state and significantly reduced total cerebral blood flow during phenylephrine-induced hypertension without reducing mean arterial blood pressure. This phenobarbital sodium effect on cerebral blood flow was not as great in the presence of acidosis, and the initial hypotensive effect of phenobarbital sodium was sustained for a longer period of time during acidosis. Phenobarbital sodium may reduce the incidence of hemorrhages in the newborn brain by providing protection against isolated hemodynamic stresses characterized by acute increases in cerebral blood flow, with or without increased mean arterial blood pressure.