Interactions between proteins and biocompatible polysaccharide have been investigated owing to their scientific and technological importance. In this study, the interactions between O-carboxymethylchitosan (OCMCS) and bovine serum albumin (BSA) are characterized by circular dichroism (CD); isothermal titration calorimetric (ITC); ultraviolet (UV) spectrum; fluorescence spectrum and transmission electron microscopy (TEM) techniques. The CID and fluorescence spectrum indicate that the conformation of BSA does not change significantly within 0.25 mg ml(-1) of OCMCS, however, higher concentration of OCMCS makes BSA denaturation. The formed composite of OCMCS and BSA shows nanospheric morphology revealed by TEM technique. The complex formation is driven by the H-bond and hydrophobic interactions. This study demonstrates that OCMCS has great potential as a matrix for delivery of the drugs such as proteins and polypeptides. (C) 2008 Published by Elsevier B.V.