The localization of manganese (Mn) and copper-zinc (Cu/Zn) superoxide dismutase (SOD)-like immunoreactive (lir) cells in the normal rat brain and the change in numbers of both SOD-lir cortical cells after the injection of ferric chloride into the sensorimotor cortex were investigated immunohistochemically. Large and medium-sized cell bodies, pyramidal to polygonal in shape, were immunostained by anti-Mn-SOD antibody. Most of these were not immunolabeled by anti-GFAP antibody, suggesting that most of the Mn-SOD-lir cells are neurons. These cell bodies were distributed in some selected brain areas with different densities. The densest population of Mn-SOD-lir cells was found in the hypothalamic and limbic structures, and in some brain stem nuclei, such as the thalamic reticular nucleus, the locus ceruleus and the pontine nucleus. Anti-Cu/Zn-SOD antibody immunostained many small round cells throughout both white and gray matter, most of which were also immunolabeled by anti-GFAP antiserum. After intacortical injection of FeCl3, the numbers of Mn- and Cu/Zn-SOD-lir cells per unit area within the adjacent narrow region of the injection site significantly increased 2 and 6 hr after the injection, respectively.