Nephrotoxicity and hepatotoxicity induced by Ochratoxin A (OTA) and ameliorating effects of melatonin were investigated in rats exposed to OTA. Experimental groups were as follows: control; OTA-treated; and OTA plus melatonin (MEL)-treated (OTA+MEL). The rats in the control group were administered with only a daily oral administration of 0.5 M NaHCO3. OTA was administered with a dose of 289 microg/kg in the same way. OTA and MEL were administered orally with OTA (289 microg/kg) and melatonin (10 mg/kg) in two different periods of time during the same day. The histopathologic changes in the liver and kidney tissues of control, OTA and OTA+MEL-treated rats were examined. There were no significant changes in the kidney and liver tissues of the control rats. Significant histopathologic changes were found in the kidney and liver tissue of rats treated with OTA. These were granular or vacuolated degeneration and necrosis of the liver cells, sinusoidal and central vein dilatation, bile duct proliferation, enlargement of periportal areas with mononuclear cell inflammatory infiltration and mild degree fibrous tissue proliferation, tubular epithelial cells degeneration, necrosis, proliferation and karyomegaly in the epithelial cells nuclei and peritubular and periglomerular lymphocyte infiltration, stromal fibrous tissue proliferation, hyperemic vessels. The severity of the lesions was significantly reduced by administration of melatonin. These results revealed that OTA induced significant histopathologic changes in liver and kidney tissue advocating OTA toxicity (P < 0.001), and administration of MEL+OTA significantly reduced the toxic effect of OTA on kidney and liver tissue of rats (P > 0.05).