Serotonin (5-HT) is a neurotransmitter that is derived from tryptophan. Owing to a hydroxyl group attached to the indole nucleus， 5-HT exhibits a considerably higher redox activity than tryptophan. To gain insight into the biological relevance of the redox activity of 5-HT， the effect of Cu(I)-binding ligands on the 5-HT-mediated copper reduction was investigated. The d-d transition band of Cu(II) complexed with glycine [Cu(II)-Gly] was not affected by addition of 5-HT alone but was diminished when a thioether-containing compound coexists with 5-HT. Concomitant with disappearance of the d-d transition band of Cu(II)-Gly， the π-π* transition band of 5-hydroxyindole of 5-HT exhibits a red-shift which is consistently explained by oxidation of 5-HT and subsequent formation of a dimeric species. The redox reactions between 5-HT and copper are also accelerated by a peptide composed of a methionine (Met)-rich region in the extracellular domain of an integral membrane protein， copper transporter 1 (Ctr1). Since Ctr1 transports copper across the plasma membrane with specificity for Cu(I)， reduction of extracellular Cu(II) to Cu(I) is required for copper uptake by Ctr1. Metalloreductases that can donate Cu(I) for Ctr1 have been identified in yeast but not yet been found in mammals. The results of this study indicate that the Met-rich region in the N-terminal extracellular domain of Ctr1 promotes the 5-HT-mediated Cu(II) reduction in order to acquire Cu(I) via a non-enzymatic process.