The activity of cytochrome-c oxidase, the terminal enzyme of the respiratory chain (complex IV), was studied at the ultrastructural level in a case of Hashimoto thyroiditis. Cytochrome-c oxidase showed a heterogeneous reaction pattern in oxyphil cells, with scattered foci of oxyphil cells lacking cytochrome-c oxidase staining. In most of the cells the defect involved all the mitochondria, but there were also oxyphil cells with a heterogeneous mitochondrial population characterized by an intracellular coexistence of mitochondria with either intact cytochrome-c oxidase or lacking activity. Immunocytochemistry further disclosed loss of mitochondrially and nuclearly encoded subunits of the enzyme. Molecular genetic analysis of mitochondrial DNA (mtDNA) revealed the presence of the 4977 base pair deletion ("common deletion") of mtDNA (8,482-13,459) in the affected areas but not in normal thyroid tissue of the patient. The amount of deleted mtDNA varied between 2 and 8% of total mtDNA. The results demonstrate that oxyphil cell change in Hashimoto thyroiditis is associated with functional and molecular genetic defects of the respiratory chain.