: OBJECTIVES: Melatonin, the major secretory product of the pineal gland, is known as an effective antioxidant and neuroprotector. Its neuroprotective actions and mechanisms have been documented in a variety of rodent brain models. However, little is known of melatonin's antioxidative capacity in the brain of primates. Herein, we investigated whether melatonin would suppress autoxidation and exogenous hydrogen peroxide-induced lipid peroxidation in monkey cerebral cortical homogenates. MATERIALS AND METHODS: The monkey brain was dissected during routine autopsy and immediately frozen at -80 degrees C until the experiment. A sample of cerebral cortex (50 mg) was homogenized in 1 ml ice cold phosphate buffer (20 mM, pH 7.4) at 0-4 degrees C. Four different treatments of cerebral cortical homogenates were performed: 1) homogenates incubated in a water bath at different temperatures (4 degrees C, 25 degrees C or 37 degrees C, respectively) for two hours to induce autoxidation; 2) homogenates co-incubated with different concentrations of melatonin at 37 degrees C for 2 hours; 3) homogenates co-incubated with 1 mM vitamin C and different concentrations of hydrogen peroxide at 37 degrees C for 1 hour to induce membrane lipid peroxidation; 4) homogenates incubated with different concentrations of melatonin and 1 mM H2O2 plus 1 mM vitamin C. After incubation, homogenates were analyzed for products of lipid peroxidation (malondialdehyde and 4-hydroxy-alkenals). RESULTS: The levels of lipid peroxidation products significantly increased in monkey cerebral cortical homogenates as a consequence of autoxidation or after the addition of H2O2 plus vitamin C. Melatonin not only suppressed the increase in lipid peroxidation induced by H2O2 plus vitamin C but also inhibited lipid breakdown resulting from autoxidation. The concentrations of melatonin required to suppress lipid peroxidation resulting from autoxidation or induced by exogenous oxidants in monkey cerebral cortical homogenates were in the same dose range. CONCLUSION: The results show for the first time that melatonin functions as an antioxidant and neuroprotector in primate brain tissue as was observed previously in rodent brain. The data provide information supporting the use of melatonin in the treatment of neurodegenerative disorders that involve oxidative damage to brain lipids.