Dynamics of cytochrome oxidase inactivation was studied in ischemic liver tissue using tetramethyl paraphenylene diamine (TMPD-oxidase) and cytochrome c (cytochrome c oxidase) as substrates. The cytochrome c ovidase activity was determined in presence of low concentrations (0.03%) of Triton X-100 (the total activity) and without the detergent (the free activity). Within 60 min after the restriction of oxygen supply to the liver tissue TMPD-oxidase was inactivated almost completely, at the same time cytochrome c oxidase maintained its activity. The free enzymatic activity became equal to the total activity; this phenomenon demonstrated an increased permeability of the external mitochondrial membrane for cytochrome c. The decrease in the TMPD-oxidase activity was considered to be due to the cytochrome c solubilization. This assumption was supported by the experiments, in which the addition of cytochrome c into the incubation mixture restored the enzymatic activity to the initial level. Hypotonic solutions and treatment of mitochondria with phospholipase A were found to simulate the impairment of the organelles in ischemic liver tissue. Increased peroxidation of unsaturated fatty acids in presence of ascorbic acid and ferrous ions was not accompanied by solubilization of cytochrome c.