Interaction of the classical coordination complex TpyCuCl₂ (Tpy = terpyridine) with cysteine was studied. Addition of cysteine to the solution of TpyCuCl₂ was found to give greatly enhanced fluorescence. UV-vis absorption and mass spectroscopic analyses were conducted to investigate this reaction under various conditions. These studies indicate that in a pure water solution (pH = 6.10–6.55), cysteine can reduce Cu(II) to generate TpyCuSCH₂CH(NH₂)CO₂H with greatly enhanced fluorescence. In a HEPES buffer solution (pH = 7.40), the Tpy ligand can be further displaced off the copper center, contributing to the enhanced fluorescence.