Prior studies have not found the alpha agonist phenylephrine, in a dose of 0.1 mg/kg, to be as effective as 0.20 mg/kg of epinephrine in improving regional cerebral blood flow (CBF) during CPR in swine. We undertook this study to assess whether higher doses of phenylephrine might improve regional CBF. Fifteen swine were allocated to receive either epinephrine 0.2 mg/kg, phenylephrine 1.0 mg/kg, or phenylephrine 10 mg/kg. Regional CBF measurements were made during normal sinus rhythm, during CPR, and during CPR following drug administration. Epinephrine 0.2 mg/kg was significantly better in improving regional CBF to the left and right cerebral cortices, cerebellum, midbrain, and cervical cord than was phenylephrine 1.0 mg/kg. There was no significant difference in regional CBF between the animals receiving epinephrine 0.2 mg/kg and phenylephrine 10 mg/kg. The study shows that large doses of epinephrine and phenylephrine may be required during CPR to improve regional cerebral blood flow following a prolonged arrest.