Melatonin protection against in vitro kainic acid-induced oxidative damage in homogenates from different rat brain regions is shown. Brain-disrupted cell homogenates from cerebral cortex, cerebellum, hippocampus, hypothalamus, and corpus striatum were incubated with kainate (11.7 mM) with or without different concentrations of melatonin (0.1-4 mM). The concentration of malonaldehyde and 4-hydroxyalkenals was measured as an index of lipid peroxidation. Wistar and Sprague-Dawley rats were used. When administered with kainate, melatonin markedly reduced lipid peroxidation in every brain region of both rat strains. The reduction in lipid peroxidation by melatonin was concentration-dependent and varied from 10% to 100%. The protection conferred by melatonin is likely due, at least in part, to its newly discovered, free radical scavenging ability.