Changes in the blood-brain barrier permeability to macromolecules were investigated during pentylenetetrazol-induced seizures, using Evans-blue as an indicator, in water-intoxicated and nonintoxicated Wistar albino (210-250 g) adult rats of both sexes. Evans-blue albumin extravasation was judged visually and estimated quantitatively with a spectrophotometer using homogenized brain to release the dye. Hypoosmolar treatment (water intoxication) was performed by the intraperitoneal administration of distilled water to a volume of 10% of the body weight; Six groups of rats were studied. Group I: female control (n=10), Group II: male control (n=10), Group III: nonwater-intoxicated female+seizure (n=15), Group IV: nonwater-intoxicated male+seizure (n=15), Group V: water-intoxicated female+seizure (n=15), Group VI: water-intoxicated male+seizure (n=15). Approximately 2 h after the injection of water, the plasma osmolarity had decreased by 25-30 mosm. Our results revealed that in female rats, the extravasation of Evans-blue albumin was greater in the brains of water-intoxicated rats compared to nonwater-intoxicated rats after pentylenetetrazol-induced seizures. In addition, hypoosmotic female rats were shown to have a larger increase in blood-brain barrier permeability than hypoosmotic male rats after pentylenetetrazol-induced seizures. This difference between male and female rats was found to be significant (P=.005).