Cyclodextrin (CD) modulated interactions between ionic surfactants with opposite charge and bovine serum albumin (BSA) at specific and nonspecific binding stages have been studied by isothermal titration calorimetry (ITC), fluorescence spectra and circular dichroism spectral measurements. At the specific binding stage with high affinity, the effectiveness of both alpha- and beta-CD for hindering BSA-SDS interactions is quite weak; however, CD is more effective in hindering BSA-CTAB specific interactions. This is due to the cooperative electrostatic and hydrophobic interaction between BSA and SDS, and to the absence of the cooperative interaction between BSA and CTAB at the specific binding stage. For both BSA-SDS and BSA-CTAB systems (especially in the former system), alpha-CD is more effective in hindering BSA-surfactant interactions than beta-CD. At the nonspecific binding stage, the addition of both alpha- and beta-CD can hinder totally both BSA-SDS and BSA-CTAB hydrophobic interactions. This is caused by the more specific hydrophobic interaction between CD and surfactant compared with the hydrophobic interaction between BSA and surfactant. Our results show that the CD effect on the protein-surfactant interaction depends on both the nature of the protein-surfactant interaction and the complexing ability of CD with surfactant. (C) 2010 Elsevier Inc. All rights reserved.