In the present study, we report the interactional behavior of the phenothiazine drug trifluoperazine dihydrochloride (TFP) with Pluronics (L64, F68, and P123) using surface tension, cloud point and fluorescence measurements. Various micellar and interfacial parameters such as critical micellization concentration (cmc), interaction parameter (beta), effectiveness of surface tension reduction (pi(cmc)), maximum surface excess concentration (Gamma(max)), and minimum area per molecule (Amin) at the air-water interface have been evaluated using surface tension technique. The phase separation behavior of the drug is studied in the presence of Pluronics, and the corresponding thermodynamic parameters such as Gibbs free energy (Delta G degrees(c)), standard enthalpy (Delta H degrees(c)), and entropy (T Delta S degrees(c)) of clouding have been calculated. Employing the steady state fluorescence measurements, the interactions between the drug and Pluronics have been determined in terms of the number of binding sites for drug molecules (n), binding constants (K-a), and Stern-Volmer quenching constants (K-sv).