It is generally postulated that amyloid-β-peptides play a central role in the progressive neurodegeneration observed in Alzheimer's disease. Important pathological properties of these peptides, such as neurotoxicity and resistance to proteolytic degradation, depend on the ability of amyloid-β-peptides to form β-sheet structures and/or amyloid fibrils. Amyloid-β-peptides are known to aggregate spontaneously in vitro with the formation of amyloid fibrils. The intervention on the amyloid-β-peptides aggregation process can be envisaged as an approach to stopping or slowing the progression of Alzheimer's disease. In the last few years a number of small molecules have been reported to interfere with the in vitro aggregation of amyloid-β-peptides. Melatonin, a hormone recently found to protect neurons against amyloid-β-peptide toxicity, interacts with amyloid-β-peptide (1–40) and amyloid-β-peptide (1–42) and inhibits the progressive formation of β-sheet and/or amyloid fibrils. These interactions between melatonin and the amyloid peptides have been demonstrated by circular dichroism (CD) and electron microscopy for amyloid-β-peptide (1–40) and amyloid-β-peptide (1–42) and by nuclear magnetic resonance (NMR) spectroscopy for amyloid-β-peptide (1–40). Our electrospray ionization mass spectrometric (ESI-MS) studies also proved that there is a hydrophobic interaction between amyloid-β-peptide (1–40) and melatonin and the proteolytic investigations suggested that the interaction took place on the 29–40 amyloid-β-peptide segment. The wide-ranging application of these results would provide further information and help in biological research. Copyright © 2001 John Wiley & Sons, Ltd.