There have been important advances in our understanding of the nuclear factors that regulate mitochondrial DNA function. Nuclear involvement in respiratory chain dysfunction is also being investigated, and evidence is accumulating that this may be more important than previously thought. In particular, the cytochrome oxidase deficiency found in senescent tissue may be caused by a nuclear rather than a mitochondrial defect. Studies continue to demonstrate a mitochondrial defect in certain neurodegenerative diseases, although controversy still surrounds the tissue distribution of such deficiencies. The relationship of such deficiencies to pathogenesis remains uncertain.