A new method was developed to measure cerebrovascular permeability to poorly permeable as well as rapidly permeable drugs. Pharmacokinetic principles for the central nervous system were established that should make it possible to calculate brain concentrations of drugs from measured plasma concentration curves. Furthermore, new criteria were established to evaluate the prescence or absence of active transport at biological membranes. It was shown that cerebrovascular integrity was not changed in protein-deprived rats, that hyperbaric 02 treatment does not alter the blood-brain barrier, and that Erythrocin B, a potentially neurotoxic food additive, does not enter the brain of conscious rats. Osmotic opening of the blood-brain barrier was charaterized in rats by autoradiographic procedures, and was successfully employed in humans with metastatic brain tumors to allow methotrexate into the brain. Neurotoxicity did not appear clinically, when cerebrovascular integrity was monitored with computer Tomography and radionuclide brain imaging. In conscious animals, blood brain barrier opening by osmotic or hypertensive means increased local cerebral glucose utilization.