We evaluated the effects of 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP-37157) (50 μM), a specific inhibitor of mitochondrial Na + /Ca 2 + exchange, applied topically onto rat cerebral cortex during ischemia-reperfusion injury. Free fatty acid (FFA) levels in cortical superfusates, withdrawn at 10 min intervals from bilateral cortical windows, were analyzed by high performance liquid chromatography. During a 20 min period of ischemia in control animals, there were significant increases in all FFAs. Following reperfusion, FFA levels remained significantly elevated. Application of CGP-37157 significantly inhibited effluxes of all FFAs during both ischemia and reperfusion. These data indicate that inhibition of mitochondrial Na + /Ca 2 + exchange likely prevented the activation of phospholipases that usually occurs following an ischemic insult as evidenced by its attenuation of FFA efflux.