mtDNA mutations and oxidative DNA damage has been observed to accumulate in the lung and other tissues in human aging. Thus, it is of interest to know whether the content of mtDNA is changed in aging tissues of the human. Using a competitive PCR method, we determined the relative content of mtDNA in the lung tissues of 49 subjects aged 16-85 years. The results showed that the relative content of mtDNA (with respect to the beta-actin gene) in the lung tissues was significantly increased with age (P < 0.005). The average mtDNA content in the lung tissues of the subjects over 80 years of age was found to be about 2.6-fold higher than that of the subjects below age 20. However, the relative content of mtDNA was slightly increased in the lung tissues of light smokers but significantly decreased in heavy smokers. Moreover, we found a significant increase with age in the level of oxidative damage to DNA as indicated by the ratio of 8-OH-dG/dG in total DNA (P < 0.0005). These results together with our previous findings suggest that the increase in mtDNA content of aging tissues may be effected through a feedback mechanism to compensate for the functional decline of mitochondria in human aging and that smoking may modulate the mechanism.