Thyrotropin-releasing hormone (TRH) forms an electroactive Cu(II) complex in aqueous solution. Rotating ring-disk electrochemistry reveals oxidation at the disk electrode and reduction at the ring electrode. The plot of limiting current vs. square root of rotation frequency deviates from the Levich equation, indicating both preceding and following chemical reactions. The reaction following the oxidation is a multiple-electron ECE-type of process that has been seen before in Cu(II)-peptide electrochemistry. The preceding reaction is unusual. The deviation from diffusion-controlled behavior is more pronounced at higher initial concentration of Cu(Il) and peptide. We propose that a non-electroactive dimer, Cu(II)(2)-TRH2, is in a slow equilibrium with the electroactive Cu(II)-TRH. Simulation of the RRDE behavior of the postulated Cu(II)-TRH system has succeeded in matching experimental data. Capillary electrophoresis indicates that there is a negative charge on the dimer. It is suggested that a hydroxo-bridge may link the two Cu(II) centers. Calculations verify that bi-nuclear Cu(II)(2)-TRH, complexes are possible. (c) 2006 Elsevier B.V. All rights reserved.