Normal ageing processes are associated with an accumulation of mutations within the mitochondrial (mt) DNA. The most frequent mutation is a 4977 base pair (bp) deletion known as common deletion. In order to test the hypothesis that chronically sun-exposed skin is characterized by an increased mutation frequency of mtDNA, the mutation frequency of the common deletion between skin and another replicating tissue (the hematopoietic system) and chronically sun-exposed versus sun-protected skin was compared in the same individuals. This was done by comparing the amount of mutated mtDNA molecules with the whole mitochondrial genome in the same specimen with a semiquantitative polymerase chain reaction method, thus allowing direct comparison of different tissues. In all skin specimens the common deletion could be observed. In contrast only 3 of 10 blood samples revealed detectable amounts of the common deletion. Comparison of sun-exposed versus sun-protected skin exhibited a higher content of the common deletion in sun-exposed skin in 7 of 10 individuals. Additionally, a hitherto undescribed mtDNA mutation was detected exclusively in human skin. These studies indicate that exposure of human skin to solar radiation leads to an accumulation of mtDNA mutations, possibly via oxidative damage, which may play an important role in photoageing.