1. It has been suggested that astrocytes prompt the induction of blood-brain barrier (BBB) functions in cerebrovascular endothelial cells. 2. In the present study we have tried to elucidate the genetic differences between astrocytes isolated from Wistar-Kyoto (WKY) control rats and astrocytes isolated from stroke-prone spontaneously hypertensive rats (SHRSP). 3. We show that endothelial cells develop tight junction-like structures, a reduction in vesicular transport and high electrical resistance when they are co-cultured with astrocytes isolated from WKY rats. In contrast, SHRSP astrocytes have less of an ability to induce BBB functions than do WKY astrocytes. 4. In addition, we demonstrate that SHRSP astrocytes produce enormous quantities of lactic acid when cerebral ischaemia develops. The decrease in pH causes astrocyte swelling and damages BBB functions. 5. Consequently, we reason that genetically weak functions in astrocytes cause disruptions of BBB function and result in widespread cerebral lesions in SHRSP.