Five children with early onset of muscle weakness, lactic acidosis and deficient cytochrome c oxidase staining in the muscle biopsy were studied. By oximetric assay of the respiratory chain of isolated mitochondria, cytochrome c oxidase deficiency was confirmed in four of the cases, while one case showed only a slight decrease of cytochrome c oxidase activity but considerably reduced activity when assayed spectrophotometrically. The muscle biopsies exhibited mitochondrial structural abnormalities and lipid storage in the four cases with oximetrically confirmed cytochrome c oxidase deficiency, while the biopsy of the case with markedly reduced activity of cytochrome c oxidase only in the enzyme-histochemical and spectrophotometrical assays had normal morphology. The light microscopical staining of cytochrome c oxidase in the four cases with oximetrically confirmed deficiency showed deficient staining of the enzyme in all extrafusal fibres in three cases but one of the cases had normal enzyme-histochemical activity of cytochrome c oxidase in about 25% of the fibres. In two cases muscle spindles were included in the biopsy. The intrafusal fibres showed normal enzyme-histochemical activity of cytochrome c oxidase. Ultrastructural examination of the enzyme distribution in two of the cases revealed great heterogeneity of the mitochondria. The structurally abnormal mitochondria were usually deficient of enzyme activity. The mitochondria of endothelial cells appeared to have normal activity. Immunohistochemical staining with polyclonal antibodies to cytochrome c oxidase revealed presence of immunoreactive material corresponding to the localisation of mitochondria in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)