Abstract : Skeletal muscle and fibroblast biopsies obtained from a normal dog and an old English sheep dog with exertional myopathy and lactic acidosis were examined for mitochondrial enzyme activities and mitochondrially coded mRNAs. The fibroblast cultures of the affected dog showed reduced cytochrome c oxidase (COX) I+II mRNA content (25% of control) and COX enzyme activities (23% of control). The skeletal muscle of the affected dog was similarly affected and showed not only decreased COX I+II mRNA content, but also decreased ATPase6 mRNA level. Apart from COX enzyme activity (62% of control), the oligomycin sensitive ATPase and NADH-Ferricyanide reductase activities were also reduced in the skeletal muscle of the affected dog (12-20% of control). These results suggest that a mitochondrial dysfunction may be the causative factor of the exertional metabolic myopathy with lactic acidosis in this affected old English sheep dog. These animals may serve as an excellent model for mitochondrial myopathies.