Thermodynamics of the binding of antibiotic streptomycin to bovine serum albumin have been studied using isothermal titration calorimetry in combination with fluorescence, UV-vis and circular dichroism spectroscopies. The Values of van't Hoff enthalpy calculated from the temperature dependence of the binding constant do nor agree with the calorimetric enthalpies indicating temperature dependent conformational changes in the protein upon binding. With increase in the ionic strength, reduction in the binding affinity of streptomycin to BSA is observed Suggesting the predominance of electrostatic interactions in the binding. The contribution of hydrophobic interactions in the binding is also demonstrated by decrease in binding affinity in the presence of tetrabutylammonium bromide (TBAB). The value of binding affinity in the presence of sucrose indicates that hydrogen bonding is not a significant contribution ill complexation. The results have permitted quantitative evaluation of the interaction of streptomycin with bovine serum albumin. (C) 2008 Elsevier B.V. All rights reserved.