Total glutathione was measured in mitochondria isolated following 30 min of ischemia and recirculation periods up to 24 h. Mitochondria prepared from the dorsolateral striatum, a region containing many neurons susceptible to short ischemic periods; were compared with those from the paramedian cortex, an ischemia-resistant region. Parallel increases in glutathione content (to approximately 150% of pre-ischemic values) were seen in both regions during the first few hours of recirculation. By 24 h of recirculation, there was a decrease below pre-ischemic values in preparations from the dorsolateral striatum but not the paramedian cortex. The early increases in mitochondrial glutathione were not associated with comparable increases in total tissue glutathione. A shorter (10 min) ischemic period also produced an early increase in mitochondrial glutathione but this was reversed more rapidly to preischemic values. The observed changes indicate post-ischemic modifications of cellular oxidative defences in the two brain regions studied.