This study was designed to investigate the preventive effect of melatonin on doxorubicin's most important side effect, cardiotoxicity. Forty male albino Wistar rats were utilized and the rats were divided into five groups: group I, 0.9% NaCl for 4 days; group II, doxorubicin 3 mg/kg/day for 4 days; group III, 2.5% ethanol for 15 days; group IV, melatonin 6 mg/kg/day for 15 days; and group V, a doxorubicin and melatonin combination were administered intraperitoneally. At the end of the experiment, tissue samples obtained from the cardiac muscle of the left ventricle of the rats were processed for measurement of malondialdehyde and for electron microscopic examination. Malondialdehyde, a product of lipid peroxidation, was found to be significantly higher in the doxorubicin group. However, in the doxorubicin and melatonin combination group the level of malondialdehyde was decreased statistical significant. The histological examination revealed destruction of myofibrils, disorganization of sarcomeres, mitochondrial degeneration and formation of giant mitochondria and lipid accumulation in the doxorubicin group. Also, accumulation of filamentous structures in the sarcoplasma in some of the cells, structural changes in capillaries and an increase in collagen fibers forming bundles were observed. When melatonin was added to the doxorubicin treatment all structural changes were reduced. The cardiotoxic side effect of doxorubicin used as a chemotherapeutic agent and was probably developed as a result of supression of the antioxidant system and lipid peroxidation. Therefore, it could be assumed that the addition of melatonin in the treatment of doxorubicin could prevent the cardiotoxicity of doxorubicin.