The analysis of human skeletal muscle mitochondria revealed a progressive decline in mitochondrial respiratory chain function with age. The activities affected to the greatest extent were those of complexes I and IV which were decreased by 59% and 47% respectively between the ages of 20-30 years and 60-90 years of age. Quantitation of the 5 kb 'common' deletion of mtDNA using PCR revealed a progressive accumulation with age, from approximately 1 in 100,000 at 21 years to 1 in 10,000 at 56 years and 1 in 5000 at 78 years of age. The low absolute levels of this mutation are unlikely to contribute significantly to the observed mitochondrial dysfunction.