Mitochondrial respiratory systems have been screened in 63 orthopaedic patients of age ranging between 17 and 91 years. The results show a statistically significant definite decrease with ageing of mitochondrial respiratory activity with pyruvate plus malate, succinate and ascorbate plus TMPD. This pattern is associated with an equally significant decrease with age of the enzymatic activity of complex I, II and IV. No significant decrease with age is, on the contrary, observed in the mitochondrial content of cytochromes a+a3, and c+c1. Preliminary Western blot analysis indicates an altered polypeptide pattern in cytochrome c oxidase. This study provides evidence for a decline with age of mitochondrial respiratory activity in human skeletal muscle, affecting complex I, II and IV.