Ochratoxin A (OTA) is a mycotoxin produced by several fungi. Many foods can be contaminated by OTA, which is consequently found in the blood of humans and animals. It is known that OTA accumulates in the brain. The aim of this study was to investigate the effects of OTA on the brain. For this purpose, the effect of OTA on N-methyl-D-aspartate (NMDA) receptor subunits 2A (NR2A) and 2B (NR2B) in the hippocampus and the protective effect of melatonin were investigated. Three groups of eight rats were used: controls, OTA-treated rats (OTA dose 289 mug/kg per day) and OTA+melatonin-trealted rats (melatonin dose 10 mg/kg per day). After four weeks of treatment, electrophoretic examinations were performed using SDS-polyacrylamide gel electrophoresis and Western blotting of hippocampal homogenates of the different groups. The concentrations of NR2A and NR2B in the OTA group were significantly lower than in the control group. The concentration of NR2B was significantly increased when melatonin was co-administered with OTA compared with OTA only. There was also a significant increase in NR2A levels when melatonin was co-administered with OTA. As a result, subchronic administration of OTA reduced hippocampal NMDA receptor subunits 2A and 2B concentrations in rats. It was thought that this alteration might affect cognitive functions because hippocampal NMDA receptors are involved in the memory and learning processes. Melatonin exhibited a partially protective effect on NR2A and NR2B against OTA.