The blood-brain barrier (BBB) in man was studied during various conditions using the indicator dilution method of Crone . Using 113m In-DTPA as reference substance the extraction, E, of the small test substances 24Na+, 36Cl-, 14C-urea and 14C-thiourea was estimated from the areas under the venous outflow curves following intracarotid slug injection of tracers. Interlaminar diffusion and red cell carriage were taken into consideration when calculating E. Cerebral blood flow (CBF) was measured using the intra-arterial 133Xe-injection method. Twenty-two patients receiving electroconvulsive therapy (ECT) were studied before and during seizures and during hypercapnia. Before seizures the extraction values in % were as follows: ENa+ 1.6, ECl- 1.9, Eurea 3.9 and Ethiourea 7.8; the corresponding values for the permeability-surface area products (PS) in ml/100 g x min were 0.5, 0.3, 0.7, 4.1, respectively. During seizure a decrease of Ethiourea and an increase of PSurea were significant. During hypercapnia PSNa and PSthiourea rose significantly. Due to the similarity of the findings in those two high flow situations it is suggested that the changes of CBF and not the epileptic activity are responsible for the changes in permeability. The mechanism of action may be a stretching of endothelial cells in the cerebral vessels or an opening up of new capillaries, or a combination of both.