We studied the relationship between the mitochondrial density in the cells and the cellular sensitivity to the toxicity of cisplatin, a potent anticancer agent. Biochemical analyses revealed that the density of mitochondria in the intestinal epithelium changed markedly along its entire length. It was the highest at the duodenum, medium at the jejunum and the lowest at the ileum. The sensitivity of epithelial cells to cisplatin toxicity was the highest at the duodenum, medium at the jejunum and the lowest at the ileum as judged from the occurrence of apoptosis. Similar correlation between the cisplatin sensitivity and mitochondrial density was also observed with in vitro experiments in which intestinal epithelial IEC-6 cells and their ⁰ cells with reduced number of mitochondria were used. The ⁰ cells had a strong resistance to cisplatin as compared with the control cells. Cisplatin markedly increased mitochondrial generation of reactive oxygen species in IEC-6 but not in ⁰ cells. We analyzed the sensitivity of 8 cell lines with different density of mitochondria to cisplatin and found the same positive correlation. These observations clearly show that cellular density of mitochondria is the key factor for the determinations of the anticancer activity and side effects of cisplatin.