The formation of oxygen metabolites (free radical species) are thought to play a role in alterations of blood-brain barrier (BBB) permeability known to occur in various neurologic disorders, including stroke and multiple sclerosis. Cerebromicrovascular endothelial cells (EC) which comprise the BBB were isolated from rat and mouse brains, cultured, and used as an in vitro model system. EC were labelled with 5lCr and exposed to free radicals generated in the presence of hypoxanthine (or xanthine) and xanthine oxidase in order to assess EC injury. The results indicated that EC, irrespective of their origin, were susceptible to free radicals generated in this system, with mouse EC being slightly more resistant than rat EC. The findings suggest that free radical species formation can lead to EC injury and may be a potential mechanism responsible for BBB permeability changes associated with various neuropathologic conditions.