Eleven patients with an established disturbance in muscle mitochondrial energy generation, in whom no defect in the pyruvate dehydrogenase complex or in the complexes of the respiratory chain could be detected, were investigated for a possible deficiency of mitochondrial creatine kinase (Mi-CK) (EC 2.7.3.2). Four patients with a defect in one of the complexes of the respiratory chain were also investigated for Mi-CK activity. In none of the investigated patients was Mi-CK deficiency found. Surprisingly, two of the four patients with a defect in one of the respiratory chain complexes showed enhanced activity of Mi-CK. It is concluded that Mi-CK deficiency is not frequently found as a primary defect in patients with disturbance in mitochondrial energy generation, but more patients should be examined to allow a definite conclusion.