The purpose of this study were 1) to determine the earliest pathological changes of germanium dioxide (GeO₂)-induced myopathy; 2) to determine the pathomechanism of GeO₂-induced myopathy; and 3) to determine the minimal dose of GeO₂ to induce myopathy in rats. One hundred and twenty five male and female Sprague-Dawley rats, each weighing about 150 gm, were divided into seven groups according to daily doses of GeO₂. Within each group, histopathological studies were done at 4, 8, 16, and 24 weeks of GeO₂ administration. Characteristic mitochondrial myopathy was induced in the groups treated daily with 10 mg/kg of GeO₂ or more. In conclusion, the results were as follows: 1) The earliest pathological change on electron microscope was the abnormalities of mitochondrial shape, size and increased number of mitochondria; 2) The earliest pathological change on light microscope was the presence of ragged red fibers which showed enhanced subsarcolemmal succinate dehydrogenase and cytochrome c oxidase reactivity; 3) GeO₂ seemed to affect the mitochondrial oxidative metabolism of muscle fibers; 4) GeO₂ could induce mitochondrial myopathy with 10 mg/kg of GeO₂ for 4 weeks or less duration in rats.