Blends of chitosan and poly(vinyl pyrrolidone) (PVP) have a high potential for use in various biomedical applications and in advanced drug-delivery systems. Recently, the physical and chemical properties of these blends have been extensively characterized. However, the molecular interaction between these two polymers is not fully understood. In this study, the intermolecular interaction between chitosan and PVP was experimentally investigated using C-13 cross-polarization magic angle-spinning nuclear magnetic resonance (C-13 CP/MAS NMR) and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). According to these experimental results, the interaction between the polymers takes place through the carbonyl group of PVP and either the OH-C-6, OH-C-3, or NH-C-2 of chitosan. In an attempt to identify the interacting groups of these polymers, molecular modeling simulation was performed. Molecular simulation was able to clarify that the hydrogen atom of OH-C6 of chitosan was the most favorable site to form hydrogen bonding with the oxygen atom of C=O of PVP, followed by that of OH-C3, whereas that of NH-C2 was the weakest proton donor group. The nitrogen atom of PVP was not involved in the intermolecular interaction between these polymers. Furthermore, the interactions between these polymers are higher when PVP concentrations are lower, and interactions decrease with increasing amounts of PVP. (c) 2008 Wiley Periodicals, Inc.