The interaction of three types of chromium(III) complexes, [Cr(salen) (H2O)(2)](+), [Cr(en)(3)](3+), and [Cr(EDTA) (H2O)](-) with AGP has been investigated. [Cr(salen) (H2O)(2)](+) [Cr(en)(3)](3+) and [Cr(EDTA) (H2O)](-) bind to Human a,-acid glycoprotein with a protein:metal ratio of 1:8, 1:6, and 1:4, respectively. The binding constant, K-b was estimated to be 1.37 +/- 0.12 x 10(5) M-1, 1.089 +/-0.05 x 10(5) M-1 and 5.3 +/- 0.05 x 10(4) M-1 for [Cr(salen) (H2O)(2)](-) [Cr(en)(3)](3+), and [Cr(EDTA) (H2O)](-), respectively. [Cr(en)(3)](3+) has been found to induce structural transition of AGP from the native twisted beta sheet to a more compact alpha -helix. The complexes, [Cr(salen) (H2O)(2)](+) and [Cr(EDTA) (H2O)](-), in the presence of H2O2, have been found to bring about nonspecific cleavage of AGP, whereas [Cr(en)(3)](3+) does not bring about any protein damage. Treatment of [Cr(salen) (H2O)(2)](+)-protein adduct with iodosyl benzene on the other hand led to site specific cleavage of the protein. These results clearly demonstrate that protein damage brought about by chromium(III) complexes depends on the nature of the coordinated ligand, nature of the metal complex, and the nature of the oxidant.