Objective: There has been some discussion as to whether the pial vasculature behaves in the same way as the blood-brain barrier as a whole. Recent studies have shown that capsazepine protects these vessels from the effects of ischemia-reperfusion. We have now used a new method to examine this protection in the whole brain. Methods: Horseradish peroxidase concentrations were measured in brain sections and plasma, following starch microsphere induced ischemia, which lasted from 20 to 60 minutes, with 30 minutes reperfusion. The PS product was calculated from the Crone-Renkin equation. Results: Permeability increase, which depended on duration of ischemia, was considerably greater in the pia than the parenchyma. The increase was also greater in tissue surrounding large radial venules of the cortex. Single vessel studies showed that these differences mirror those between small and large pial venules. Capsazepine treatment protected the parenchymal blood-brain barrier by limiting the post-ischemic permeability increase to about one third, but had no effect on the pia or radial vessel permeability. Conclusions: Permeability has been estimated in tissue sections with good spatial resolution using this new technique, which has demonstrated that the TRPV1 receptor plays an important role in the whole brain, not confined to small pial venules.