Abstract Studies with isolated skeletal muscle mitochondria from a human subject with severe hypermetabolism of non-thyroid origin are reported. 1. 1. In confirmation of earlier observations in the same patient, these mitochondria almost completely lack respiratory control. Respiration is virtually independent of both inorganic phosphate and adenosine diphosphate, and it is insensitive to oligomycin. The mitochondria exhibit an oxidative phosphorylation with a phosphate/oxygen ratio which is somewhat below the normal value. 2. 2. The above anomalies are shown to occur to largely the same extent in two subfractions of the mitochondrial population, containing “large” and “normal-sized” mitochondria, respectively. 3. 3. The cell-sap fraction from the patient's muscle exhibits no uncoupling effect on normal mitochondria. 4. 4. The ubiquinone content of the patient's muscle is normal. Some implications of the findings for the functional and etiological aspects of the mitochondrial defect studied and for the biochemical mechanism of mitochondrial respiratory control in general are discussed.