SUMMARY Using the "double indicator" technique the ability of 3 H-isoproterenol and "C-propranolol to cross the blood-brain barrier was studied in man. In 3 subjects extraction of isoproterenol was 3.8% in a single passage and the PS product was 2.0 ml/lOOg/min. In 4 patients extraction of propranolol was 63% and PS was 46.7 ml/100/min. Regional cerebral blood flow (rCBF) was studied in man with the 133 Xe-intraarterial injection method. Intracarotid isoproterenol (3 /xg/min., 6 patients) caused a significant reduction in rCBF, but after correction for a concomitant decrease in arterial Pco 2 the alteration was no longer significant (59.8 -51.7/57.4 ml/100g/min.). Intracarotid propranolol (0.15 mg/kg, 11 patients) caused no significant change in rCBF, but after correction for arterial Pco 2 change the alteration although only 4% was just significant,/? < 0.05. (56.3-55.8/54.1 ml/lOOg/min). After propranolol the rCBF changes caused by alterations in the arterial Pco 2 were normal and the focal flow increase during hand work could not be changed by simultaneous intracarotid propranolol.RECENT scientific investigations have dealt with the effects of cervical sympathetic nerve stimulation/section or with the pharmacology of the cerebrovascular a-adrenergic receptor mechanisms. This extensive literature is somewhat contradictory, but increasing evidence supports the contention that sympathetic nerves via a-receptors play a significant role in the tone of brain vessels under certain circumstances. For the most recent studies see Edvinsson and McKenzie.