Combined histochemical and biochemical studies have shown, that the histochemical activity of mitochondrial Mg2+-activated ATPase closely correlates with the coupling state of oxidative phosphorylation (Meijer and Vloedman 1980). Using this histochemical method 646 unselected skeletal muscle biopsies have been investigated. Activation of the enzyme, i.e. loosely coupled mitochondria were present either focally or diffusely expressed in 28% of the biopsies irrespective of the underlying disorder. Most often it was found in mitochondrial myopathies and in progressive muscular dystrophy type Duchenne; in a lesser degree it was also present in neurogenic atrophy and in various other disorders. Ninety two percent of all cases with loose coupling showed mitochondrial proliferations. On the other hand in 20% of all cases with mitochondrial proliferations including 19 cases of diffuse mitochondrial myopathy and 3 of progressive external ophthalmoplegia no activation of the enzyme was found. The results show that loose coupling is closely but not absolutely associated with mitochondrial proliferation, it is present in mitochondrial myopathies but also in various other muscular disorders with different pathogenesis.