To study the effects of melatonin on primary rat cortico-hippocampal neurotoxicity induced by amyloid beta-peptide 25-35. METHODS: The neuronal mor-phology was observed by phase-contrast microscopy. The iw.urotoxieity was quantitatively estimated by measur-ing laclate duhydrogenase (LDH) released into the culture medium from the damaged neurons. The neuronal metabolic state was quantified by the reduction of 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazo1ium bromide (MTr). RESULTS: Treatment ofprimary rat cortico-hipocampal neuonns with amyloid beta-peptide 25-35 (20 μmol/L) for 24h caused a significant decrease in neurocyte viability (P<0.01, compared with control). Melatonin (1 or 10 μmol/L) reduced the neurotoxicity induced by amyloid beta-peptidu 25-35. CONCLU-SION: Amyloid beta-peptide 25-35 could exert direct cytotoxicity on rat cortico-hippocampal neurocytes and melatonin concerdration-dependently rescued cultured neurons from exposure to amyloid beta-peptide 25-35 induced injury.