To clarify the role of oxygen free radicals in expression of the c-fos protooncogene, the distribution of c-fos mRNA was investigated in CuZn-superoxide dismutase (SOD-1) transgenic (Tg) mice compared to control nontransgenic (nTg) littermates after a mild (i.e. 10 min) focal cerebral ischemia. c-fos mRNA expression occurred at 1 to 6 h after reperfusion in the ipsilateral hippocampus and thalamus in Tg mice, whereas it did only at 1 h in the same regions in nTg mice. In the ipsilateral cortex, there were no significant differences in the pattern of the expression between nTg and Tg mice. These results suggest that oxygen radicals may suppress the expression of c-fos in the hippocampus and thalamus, the areas known to be without blood supply from the middle cerebral artery, following a mild focal cerebral ischemia and reperfusion.