Aim: To observe the impact of beta-amyloid (Aβ) on nitric oxide (NO) levels of nervous tissue and cultured neuronal cells from rats and the antagonistic role of melatonin. Methods: The experiment was carried out in the Laboratory of Psychiatric Department, West China Hospital of Sichuan University from June to November 2000. 1 Aβ and melatonin were exposed to cultured neuronal cells from rats. 2 Aβ25-35 was microinjected into hippocampus and melatonin intraperitoneally injected into rats. 3 NO level and nitric oxide synthase (NOS) activity from brain tissue and cultured neuronal cell were measured by chromatometry. Results: The Aβ increased the level of NO and the activity of NOS of brain tissue and cultured neuronal cell, showing a positive correlation with the concentration of Aβ (r = 0.786, P < 0.01). The levels of NO were (7.9 ± 1.3), (9.2 ± 1.5), (12.6 ± 2.4), (14.1 ± 1.4) μmol/L respectively exposed to 0.5, 1.0, 10.0, 20.0 μmol/L Aβ, which was significantly different from that of the control group [(5.9 ± 1.4) μmol/L]. Melatonin decreased the level of NO and the activity of NOS induced by Aβ. Conclusion: NO is involved in the neurotoxic effects induced by Aβ; Melatonin is in part against the neurotoxicity of Aβ by reducing the level of NO and the activity of NOS.