Using the "double indicator" technique the ability of 3H-isoproterenol and 14C-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/100g/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 133Xe-intraarterial injection method. Intracarotid isoproterenol (3 migrogram/min., 6 patients) caused a significant reduction in rCBF, but after correction for a concomitant decrease in arterial PCO2 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 PCO2 change the lateration although on 4% was just significant, p less than 0.05. (56.3 -55.8/54.1 ml/100g/min). After propranolol the rCBF changes caused by alterations in the arterial PCO2 were normal and the focal flow increase during hand work could not be changed by simultaneous intracarotid propranolol.