alpha-Tocopherol (alpha-TC) is considered an important endogenous brain antioxidant. The utility of brain alpha-TC levels as an index of in vivo lipid peroxidation has recently been suggested. Therefore, we explored the significance of alpha-TC levels in brains to ischemic insults associated with global or focal cerebral ischemia. Four ischemic models were used and alpha-TC was measured by HPLC. Brain alpha-TC levels in gerbils exposed to 20 min bilateral carotid artery occlusion (CAO) and 60 min reperfusion was 10.8 +/- 2.1 micrograms/g (x +/- S.D., n = 6) vs. 10.8 +/- 1.8 micrograms/g (n = 6) in sham controls. In gerbils subjected to 3 h unilateral CAO and 2 h RP, a procedure marked by neurological abnormalities, brain alpha-TC levels of ischemic and non-ischemic hemispheres were essentially the same (10.7 +/- 1.6 vs. 10.1 +/- 1.4 micrograms/g, n = 4). In rats subjected to 80 min unilateral middle cerebral artery occlusion followed by 60 min reperfusion, or 6 h occlusion without reperfusion, the brain alpha-TC levels in ipsilateral ischemic and contralateral non-ischemic cortex were not different (12.1 +/- 1.2 vs. 11.9 +/- 2.6 micrograms/g or 12.2 +/- 1.6 vs. 13.4 +/- 1.2 micrograms/g, n = 4-8). Our results demonstrated that brain alpha-TC levels can not be used as index of ischemia/reperfusion related lipid peroxidation or tissue injury.