The physiological roles of the pineal hormone melatonin are still not completely clarified. Recently it has been shown that melatonin is a potent, endogenous scavenger of reactive oxygen species suggesting that it might interfere with neurodegenerative processing involving free-radical formation and excitatory aminoacid release. These neuroprotective effects of melatonin may result, at least in part, from a sparing of glutathione reductase, which is decreased following administration of the neurotoxic agent kainate (KA) in rats. Moreover, KA causes a rapid decrease in glutathione (GSH) content of cultured cerebellar granule neurons but not in astrocytes. These cell types both express functional KA receptors, but only the former is sensitive to reactive oxygen species-dependent KA injury. Melatonin counteracts the changes in GSH, induced by KA, in cultured cerebellar granule neurons.