Photocatalytic degradation kinetics of antivirus drug-lamivudine in aqueous TiO2 dispersions was systematically optimized by both single-variable-at-a-time and central composite design based on the response surface methodology. Three variables, TiO2 content, initial pH and lamivudine concentration, were selected to determine the dependence of degradation efficiencies of lamivudine on independent variables. Response surface methodology modeling results indicated that degradation efficiencies of lamivudine were highly affected by TiO2 content and initial lamivudine concentration. The highest degradation efficiency was achieved at suitable amount of TiO2 and with maintaining initial lamivudine concentration to a minimum. In addition, the contribution experiments of various primary reactive species produced during the photocatalysis were investigated with the addition of different scavengers and found that hydroxyl radicals was the major reactive species involved in lamivudine degradation in aqueous TiO2. Six degradation intermediates were identified using HPLC/MS/MS, and photocatalytic degradation mechanism of lamivudine was proposed by utilizing collective information from both experimental results of HPLC/MS/MS, ion chromatography as well as total organic carbon and theoretical data of frontier electron densities and point charges. (C) 2011 Elsevier B.V. All rights reserved.