Combined spectrophotometric and computer-based pH-metric investigations on the mixed-ligand complex formation equilibria of CuII with histidine [(C3H3N2)CH2CH(NH2)COOH, hisH±] and biguanide [NH2C-(=NH)NHC(=NH)NH 2, Bg] in aqueous solution at a constant ionic strength (I = 0.1 mol dm-3) and 25 ± 1°C, provided evidence of binary [Cu(hism)+], [Cu(hism-H)], [Cu(hism)2], [Cu(hism)(hism-H)-], [Cu(hism-H)22-] and [Cu(Bg)2+] and ternary [Cu(hism)(Bg)+], [Cu(hism-H)(Bg)], [Cu(Bg)(OH)+] and [Cu(Bg-H)(OH)] complexes. Histidine provides both histamine-like [(NH2, N-imidazole i.e. (hism-)] and mixed histamine-like glycine-like [(NH2, N-imidazole) (NH2, COO-) i.e. (hism-)(gly-)] chelation, barring simple glycine-like (gly-) chelation. Binding affinity of Cu II for (NH2, =NH) bidentate chelating biguanide is so strong that the histidine-imidazole deprotonated mixed-ligand complex, [Cu(hism-H)(Bg)] decomposes at pH > 10 to biguanide (=NH) deprotonated ternary hydroxo complex, [Cu(Bg-H)(OH)], setting free the his- ligand ion in solution, a phenomenon of great biological significance, in regard to medicinal applications of the title ligands and their metal derivatives.