The present study aims to evaluate the possible preventive effect of melatonin against dimethyl-benz(a)anthracene (DMBA) induced cell proliferation and DNA synthesis in epithelial cells of cortical and medullary renal tubules in mice applying the method of quantitative autoradiography. Exposure to a single injection of DMBA (10mg/ 100g b.w.) and examined after 60 days revealed different changes in cell proliferation in the two portions of the tubules. In males, the mean values raised by 388% and 363% for cortical and medullary renal tubules respectively compared to control. The mean grain count over labelled nuclei was reduced 51% and 35.2% respectively for the two portions of the renal tubules. In females the cell division was stimulated by 125% in the cortical tubules and whereas in the medullary portion it remained nearly unchanged compared to control. In males, the mean grain count over labelled nuclei was lower by 47.6% in cortical renal tubules and by 67.3% in medullary renal tubules. In females, the mean grain count over labelled nuclei was in both portions reduced by about 60%. Long term exposure to a single injection of DMBA for 120 days increased the cell proliferation in males and females in both portions of the renal tubules. A daily melatonin injection (100 μg/ 100g b.w.) for 60 and 120 days proliferation rate by 79.8% and 83.9% respectively in males for the two portions, while the mean grain count over labelled nuclei was lower by 20% and 39% respectively. In females melatonin attenuated cell proliferation by 67% and 43% in cortical and medullary respectively compared to the DMBA exposed group. and reached thereby the level of control. The grain counts over labelled nuclei were reduced identically by 105% in cortical and medullary renal tubules, but remained still 20% under that of control.