We have investigated the role of mitochondria on an active cell death, a feature of apoptosis, under the oxygen stress. An immortalized human fibroblast cell line (rho+) carrying normal mitochondrial genome (mtDNA) underwent an active cell death in 95% oxygen; 68% and 84% of the cells died on the 3rd and 4th days, respectively. By contrast, its derivative lacking mtDNA (rho 0) exhibited a marked resistance to cell death. PCR analyses using 180 primer pairs covering the entire regions of the mtDNA revealed extensive fragmentations of the mtDNA; 49 types of deletions increased up to 187 on the 3rd day. These results indicate that mtDNA and its fragmentation are the underlying molecular lesions in a cell death pathway induced by the oxygen stress.