Subpial injection of aqueous solutions of iron salts into rat isocortex induces recurrent epileptiform discharges with focal brain edema, cavitary necrosis and gliosis. Since aqueous iron or heme compounds cause peroxidation of lipids, we studied the sequence of changes in the formation of free radicals, and superoxide radicals, in rat isocortex injected with 5 μl of 100 mM FeCl₃. Electron spin resonance measurements of whole rat brain showed a transient increase in heme-bound Fe³⁺. Superoxide radicals were increased in a cylinder of tissue obtained at the injection site 5 min and 15 min after completion of the injection. This study shows that iron salts injected into rat isocortex cause transient formation of free radicals. We suggest that decompartmentalization of iron compounds may be of importance in trauma-related brain injury responses.