We investigated immunohistochemically the localization and changes of manganese superoxide dismutase (Mn-SOD) in substantia nigra after 1 h of middle cerebral artery (MCA) occlusion in the rat with reperfusion periods of 1, 3, 7, and 14 days. In normal rats, Mn-SOD immunoreactivity was observed intensely in many large neurons in substantia nigra pars reticulata (SNr) and weakly in neurons in the pars compacta (SNc). The immunoreactivity of the neurons in both SNr and SNc was reduced after 1 day and almost lost 3 days after MCA occlusion, although these neurons showed completely normal morphology. The immunoreactivity recovered only in the large neurons in SNr from the 7th day and well preserved after 2 weeks, when SNr showed obvious atrophy. The results indicate that oxidative stress may be involved in the pathogenesis of the secondary postischemic neurodegeneration in SN.