Regional superoxide dismutase (SOD) activity and lipid peroxidation (as reflected by thiobarbituric acid-reactive substances (TBARS)) have been measured at increasing post-ischemic time intervals following a (10 min) forebrain ischemic insult in rat. All brain regions showed significant progressive increases in SOD activity with increasing post-ischemic time intervals. Lipid peroxidation also was significantly increased in frontal and parietal/occipital regions at 1 and 24 h post-ischemia, although this was several orders of magnitude less than the increase in SOD activity. By 7 days post-ischemia lipid peroxidation had returned to control values for all regions. These data are consistent with the hypothesis that cerebral ischemia is accompanied by glial activation with an associated increase in SOD activity. Global increases in SOD activity may protect the brain from free radicals, thereby preventing large increases in lipid peroxidation.