Aggregation of the beta-amyloid (Aß) peptide is associated with the development of Alzheimer’s disease. Recent research has focused on identifying small molecular aggregation inhibitors. Several indole derivatives have been shown to inhibit aggregation of Aß. (Cohen, et al., Biochem, 45 (2006) p. 4727) Of particular interest is melatonin, which occurs naturally, and 4-hydroxyindole (4-HI), which displays strong anti-amyloidogenic properties. It remains largely unknown how the interaction of these molecules prevent or promote aggregation of the peptide. Based upon proposals that indole derivatives bind to Ab’s three histidine residues (Pappolla, et al., J Biol Chem 273 (1998) p. 7185), we have employed UV resonance Raman (UVRR) spectroscopy to monitor the interaction of both melatonin and 4-HI with histidine. The UVRR spectra of the indole derivatives are readily visible and similar to that of the amino acid tryptophan, which is lacking in the Ab peptide.  Thus, the UVRR spectrum of indole derivatives may be used to identify interaction sites on the indole compounds. Preliminary studies suggest differential binding mechanisms for melatonin and 4-HI.