We have investigated the dynamics of cytochrome c oxidase (COX) activity in the cerebrospinal fluid (CSF) and the erythrocyte haemolysate (EH) in 85 patients suffering from brain infarction (BI), reversible (RIA), or transient (TIA) ischemic attack from the perspective of mitochondrial affection in ischemia. In all patients, the COX activity was decreased in the CSF, especially within the first two days, indicating an acute inactivation or modification of mitochondrial proteins, probably mediated by free radicals. The gradual elevation of COX activity until the seventh day suggested that these changes may be reversible. The increase in the COX activity was established in the EH, with the highest values found in the BI, somewhat lower in the RIA, and the lowest in the TIA group, respectively. This could indicate a systemic compensatory response to an acute ischemia. Thus, COX activity in the CSF and EH in acute ischemia could be an indicator of brain metabolic dysfunction.