The behaviour of brain capillary endothelium to the passage of macromolecules in single and repeated seizures conditions and its relationship to the brain trace element concentrations are the main subject of this study. For this purpose, animals were treated with either single or repeated doses of pentylenetetrazole (PTZ). As a marker of blood-brain barrier (B-BB) permeability changes, Evans Blue (EB) dye was used. Seizure activity was observed and seizure patterns and convulsion times were recorded. PTZ treatment induced generalised tonic-clonic seizure in all animals, but seizures were found to be lasting longer in single seizure group than repeated seizures group. Seizures induced by single dose PTZ treatment resulted in bilateral EB leakage in the preoptic area, caudate nucleus, putamen, thalamus, hypothalamus, midbrain, and the superior colliculus. However, repeated PTZ-induced seizures led to EB leakage in the brains of only few number of rats, and it was confined to hypothalamus, caudate nucleus, cerebellum, thalamus, and pons. On the other hand, while the levels of copper (Cu) and iron (Fe) in brain tissue were found to be decreased significantly in the repeated seizures group when compared with the other groups, the levels of zinc (Zn) did not show any differences between groups. These results indicate that the regional B-BB opening markedly differs between single and repeated PTZ-induced seizures group and this difference may be due to PTZ tolerance and changes in cerebral endothelial structure. (C) 2003 Elsevier Science Ltd. All rights reserved.